alcoholism thesis statement

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Alcoholism research paper: writing guide & topics.

Writing a research paper on alcoholism might seem like pushing a cart downhill; nevertheless, most students end up feeling frustrated. The need to bring out a new and captivating piece, in the end, remains a dream to many. But luckily, there’s a way out!

Read the sections that follow and forget about alcoholism research paper hangovers and blackouts.

How To Write an Alcoholism Research Paper Thesis

As earlier introduced, knowing the secret behind any successful paper puts you in the winning team. We need to note that such an article will majorly serve two essential purposes:

• To fight alcoholism
• To raise awareness among the people

The alcoholism outline for the research paper is as follows:

Alcoholism Research Paper Intro

An exciting introduction will hook the reader to your research paper. He/she will want to read more to feed his curiosity. Since the intro is the first paragraph that meets the reader’s eye, it should be outstanding as much as possible.

You can spice up your introduction in the following ways:

Present unexpected statistics and facts on alcoholism, Brief definitions of technical terms in your topic, if any Give the context of your research through background information Add a clear and precise thesis statement

The thesis statement serves as an anchor for your paper, determining your stance on the subject. Therefore, keep it short and sweet yet communicating the main point coherently.

It consists of all the arguments in support of your thesis statement. For a strong defense, ensure that you line up your undisputed and important ideas first as you move to the least. Some of the alcoholism research paper points to include in your body can be:

• Social effects of alcoholism on students
• How to help people struggling with alcoholism
• Symptoms of alcoholism in teenagers

Arrange the points in an orderly way so that your reader can follow through quickly. Each body paragraph should have a well-stated topic sentence, followed by an elaborate explanation and relevant examples.

Conclusion For Alcoholism Research Paper

After presenting your case on alcoholism and defending it with supporting arguments, it’s time, to sum up, your paper. The conclusion for alcoholism research paper summarizes the discussion in short, clear, and precise sentences.

You should also restate the thesis statement to emphasize your main idea of the paper. In conclusion, the general rule of thumb applies, do not add any new information. Strife to make it as short as possible yet not devoid of meaning.

When writing papers on alcoholism, be sure to use factual arguments, especially for the symptoms, effects, and other related statistics. Remember to be sensitive to the choice of words not to end up stigmatizing your reader.

Whether it’s a paper on addiction or withdrawal symptoms, do not vocabularies that may blur the reader from the article’s full picture.

Below are professionally handpicked alcoholism research paper topics for your inspiration:

Teenage Alcoholism Research Paper Topics

• Why do most teens think drinking alcohol is cool?
• Reasons why most students in college’ want to fit in.’
• Do parents who drink influence the teens also to start the habit?
• Does alcohol make teens feel more comfortable around their friends?
• Can alcohol raise the self-esteem of teens?
• Why many teens opt for alcohol when they feel pressured
• What are the withdrawal symptoms for teens addicted to alcohol?
• How teens can battle anxiety and depression without taking alcohol

Topics For Research Paper on Alcoholism and Family

• How alcohol makes parents neglect their essential duties
• Why forgetfulness as a result of alcoholism may disrupt family relationships
• Domestic violence as a result of excessive alcohol drinking
• Financial instability in families with alcohol addicts
• Can parents who drink alcohol help their children with homework?
• Why do children from families where parents drink alcohol suffer depression?
• Difficulty with intimate relationships among adults who drink alcohol
• Mental and physical health issues as a result of alcoholism in the family

Topics on Risks of Alcoholism

• Motor vehicle accidents arising from drinking and driving
• Why cases of homicide are on the rise among those who drink
• What causes alcohol poisoning?
• Risky sexual behaviors as a result of irresponsible drinking
• How mothers can experience miscarriage if they take excessive alcohol consumption
• Why do alcohol drinking people develop high blood pressure?
• Learning and memory difficulties as a result of alcoholism
• Why you risk losing your job if you continue drinking

Topics on Alcoholism as a Disease

• Can we classify alcoholism as a curable disease?
• The pre-alcoholic phase of alcoholism as a disease
• What is the relationship between increased heart rate and alcoholism?
• How effective is the Intensive Outpatient alcoholism treatment Program?
• Causes of relapse among patients recovering from alcoholism
• Aftercare support programs for patients dealing with alcoholism
• How scary is a diagnosis of alcoholism?
• Medical treatment options for people struggling with alcohol addiction

Alcohol Abuse Research Paper Topics

• The impact of alcohol abuse on relationships
• How alcohol abuse can cause harm or injury
• How alcohol abuse can harm the quality of your life
• Sexual dysfunction complications as a result of alcohol abuse
• Recommended ways of controlling alcohol abuse
• Medications to reduce the symptoms of withdrawal among addicts
• The role of support groups in reducing alcohol abuse
• Warning signs that you are abusing alcohol

Addiction Research Paper Topics

• Why is the youthful population the most affected with alcohol addiction?
• Best approaches to dealing with alcohol addiction among adults
• How drug addiction has led to increased crime rates in society
• Does counseling help to deal with the problem of drug addiction?
• Compare and contrast drug addiction between first and third world countries
• What measures can the government institute curb drug addiction?
• How drug addictions contribute to marriage breakups
• Why most drug addicts cannot have gainful employment opportunities
• How alcohol addiction impacts human health
• Why are the majority of street children drug and substance addicts?
• What are the policies legislating against drug addiction?
• Why are more men drug addicts than women?
• Rehabilitation systems of helping drug addicts
• Sociological perspectives of drug addiction
• A step by step approach to helping adolescents in drug addiction

In case the topics are not enough for you, we have professional research paper writing help for college students. Using our services will ensure that you attain that much-coveted A+.

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The Palgrave Handbook of Psychological Perspectives on Alcohol Consumption pp 25–50 Cite as

Psychological Theories of Alcohol Consumption

• Richard Cooke 8 , 9  
• First Online: 11 May 2021

1056 Accesses

1 Citations

This chapter begins with an outline of several psychological theories of alcohol consumption, including alcohol expectancy theory, the cognitive model of binge drinking, incentive motivation model, and the theories of reasoned action and planned behaviour, which have been proposed to account for alcohol consumption. An outline of each theory is provided before the evidence base for each is reviewed. Next, the chapter compares and contrasts the theories in terms of evidence before considering theoretical overlap between constructs and outlining studies that have tested multiple theories in the same sample. After a brief discussion of theoretical integration, a number of methodological issues with existing tests of theories are outlined and discussed. The chapter ends with suggestions for future research.

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Ajzen, I. (1991). The theory of planned behavior. Organizational Behavior and Human Decision Processes, 50 , 179–211. https://doi.org/10.1016/0749-5978(91)90020-T

Article   Google Scholar  

Ajzen, I. (1996). The directive influence of attitudes on behavior. In P. M. Gollwitzer & J. A. Bargh (Eds.), Psychology of action (pp. 385–403). New York, NY: Guildford Press.

Google Scholar  

Ajzen, I. (2002). Perceived behavioral control, self-efficacy, locus of control, and the theory of planned behavior. Journal of Applied Social Psychology, 32 , 665–683.

Ajzen, I., & Fishbein, M. (1973). Attitudinal and normative variables as predictors of specific behaviors. Journal of Personality and Social Psychology, 27 , 41–57.

Ajzen, I., & Sheikh, S. (2013). Action versus inaction: Anticipated affect in the theory of planned behavior: Anticipated affect. Journal of Applied Social Psychology, 43 (1), 155–162. https://doi.org/10.1111/j.1559-1816.2012.00989.x

Atwell, K., Abraham, C., & Duka, T. (2011). A parsimonious, integrative model of key psychological correlates of UK university students’ alcohol consumption. Alcohol and Alcoholism (Oxford, Oxfordshire), 46 (3), 253–260. https://doi.org/10.1093/alcalc/agr016

Article   PubMed   Google Scholar  

Bandura, A. (1977). Self-efficacy: Toward a unifying theory of behavioral change. Psychological Review, 84 (2), 191–215.

Burgess, M., Cooke, R., & Davies, E. L. (2019). My own personal hell : Approaching and exceeding thresholds of too much alcohol. Psychology & Health, 34 (12), 1451–1469. https://doi.org/10.1080/08870446.2019.1616087

Cameron, D., Epton, T., Norman, P., Sheeran, P., Harris, P. R., Webb, T. L., … Shah, I. (2015). A theory-based online health behaviour intervention for new university students (U@Uni:LifeGuide): Results from a repeat randomized controlled trial. Trials, 16 . https://doi.org/10.1186/s13063-015-1092-4

Cooke, R., Bailey, O., Jennings, J., Yuen, C., & Gardner, B. (2020). Do preparatory behaviours predict alcohol consumption among UK university students? British Journal of Health Psychology , https://doi.org/10.1111/bjhp.12489

Cooke, R., Beccaria, F., Demant, J., Fernandes-Jesus, M., Fleig, L., Negreiros, J., Scholz, U., & de Visser, R. (2019). Patterns of alcohol consumption and alcohol-related harm among European university students. European Journal of Public Health , ckz067. https://doi.org/10.1093/eurpub/ckz067 .

Cooke, R., Beccaria, F., Demant, J., Fernandes-Jesus, M., Fleig, L., Scholz, U., & de Visser, R. O. (2021). Predicting alcohol consumption among European university students using data from the CALIBRATE study. Unpublished manuscript

Cooke, R., Dahdah, M., Norman, P., & French, D. P. (2016). How well does the theory of planned behaviour predict alcohol consumption? A systematic review and meta-analysis. Health Psychology Review, 10 , 148–167. https://doi.org/10.1080/17437199.2014.947547

Cooke, R., Sniehotta, F., & Schuz, B. (2007). Predicting binge-drinking behaviour using an extended TPB: Examining the impact of anticipated regret and descriptive norms. Alcohol and Alcoholism, 42 (2), 84–91. https://doi.org/10.1093/alcalc/agl115

Cooper, M. L. (1994). Motivations for alcohol use among adolescents: Development and validation of a four-factor model. Psychological Assessment, 6 (2), 117–128. https://doi.org/10.1037/1040-3590.6.2.117

Cooper, M. L., Krull, J. L., Agocha, V. B., Flanagan, M. E., Orcutt, H. K., Grabe, S., … Jackson, M. (2008). Motivational pathways to alcohol use and abuse among Black and White adolescents. Journal of Abnormal Psychology, 117 (3), 485–501. https://doi.org/10.1037/a0012592

Cooper, M. L., Kuntsche, E., Levitt, A., Barber, L. L., & Wolf, S. (2015). Motivational models of substance use: A review of theory and research on motives for using alcohol, marijuana, and tobacco. In K. J. Sher (Ed.), The Oxford handbook of substance use disorders (Vol. 1). Oxford, England: Oxford University Press. https://doi.org/10.1093/oxfordhb/9780199381678.013.017

Chapter   Google Scholar  

Cox, W. M., & Klinger, E. (1988). A motivational model of alcohol use. Journal of Abnormal Psychology, 97 (2), 168–180.

Epton, T., Norman, P., Dadzie, A.-S., Harris, P. R., Webb, T. L., Sheeran, P., … Shah, I. (2014). A theory-based online health behaviour intervention for new university students (U@Uni): Results from a randomised controlled trial. BMC Public Health, 14 . https://doi.org/10.1186/1471-2458-14-563

Fearnow-Kenney, M., Wyrick, D. L., Milroy, J. J., Reifsteck, E. J., Day, T., & Kelly, S. E. (2016). The effects of a web-based alcohol prevention program on social norms, expectancies, and intentions to prevent harm among college student-athletes. The Sport Psychologist, 30 , 113–122.

Fernandes-Jesus, M., Beccaria, F., Demant, J., Fleig, L., Menezes, I., Scholz, U., … Cooke, R. (2016). Validation of the drinking motives questionnaire—Revised in six European countries. Addictive Behaviors, 62 , 91–98. https://doi.org/10.1016/j.addbeh.2016.06.010

Foster, D. W., Dukes, K., & Sartor, C. E. (2016). The road to drink is paved with high intentions: Expectancies, refusal self-efficacy, and intentions among heavy drinking college students. Alcohol, 50 , 65–71. https://doi.org/10.1016/j.alcohol.2015.11.004

French, D. P., Cooke, R., Mclean, N., Williams, M., & Sutton, S. (2007). What do people think about when they answer theory of planned behaviour questionnaires?: A ‘think aloud’ study. Journal of Health Psychology, 12 (4), 672–687. https://doi.org/10.1177/1359105307078174

Gardner, B., de Bruijn, G.-J., & Lally, P. (2012). Habit, identity, and repetitive action: A prospective study of binge-drinking in UK students: Habit, identity, and repetitive action. British Journal of Health Psychology, 17 (3), 565–581. https://doi.org/10.1111/j.2044-8287.2011.02056.x

Goldsmith, A. A., Thompson, R. D., Black, J. J., Tran, G. Q., & Smith, J. P. (2012). Drinking refusal self-efficacy and tension-reduction alcohol expectancies moderating the relationship between generalized anxiety and drinking behaviors in young adult drinkers. Psychology of Addictive Behaviors, 26 (1), 59–67. https://doi.org/10.1037/a0024766

Gray, J. A. (1970). The psychophysiological basis of introversion-extraversion. Behavior Research and Therapy, 8 , 249–266.

Hasking, P., Boyes, M., & Mullan, B. (2015). Reward and cognition: Integrating reinforcement sensitivity theory and social cognitive theory to predict drinking behavior. Substance Use & Misuse, 50 (10), 1316–1324. https://doi.org/10.3109/10826084.2015.1005315

Hauck-Filho, N., Teixeira, M. A. P., & Cooper, M. L. (2012). Confirmatory factor analysis of the Brazilian version of the Drinking Motives Questionnaire-Revised (DMQ-R). Addictive Behaviors, 37 (4), 524–527. https://doi.org/10.1016/j.addbeh.2011.11.023

Kuntsche, E., & Cooper, M. L. (2010). Drinking to have fun and to get drunk: Motives as predictors of weekend drinking over and above usual drinking habits. Drug and Alcohol Dependence, 110 (3), 259–262. https://doi.org/10.1016/j.drugalcdep.2010.02.021

Leigh, B. C., & Stacy, A. W. (1993). Alcohol outcome expectancies: Scale construction and predictive utility in higher order confirmatory models. Psychological Assessment, 5 (2), 216–229. https://doi.org/10.1037/1040-3590.5.2.216

Morawska, A., & Oei, T. P. S. (2005). Binge drinking in university students: A test of the cognitive model. Addictive Behaviors, 30 (2), 203–218. https://doi.org/10.1016/j.addbeh.2004.05.011

Newton, N. C., Barrett, E. L., Swaffield, L., & Teesson, M. (2014). Risky cognitions associated with adolescent alcohol misuse: Moral disengagement, alcohol expectancies and perceived self-regulatory efficacy. Addictive Behaviors, 39 (1), 165–172. https://doi.org/10.1016/j.addbeh.2013.09.030

Norman, P. (2011). The theory of planned behavior and binge drinking among undergraduate students: Assessing the impact of habit strength. Addictive Behaviors, 36 (5), 502–507. https://doi.org/10.1016/j.addbeh.2011.01.025

Norman, P., Bennett, P., & Lewis, H. (1998). Understanding binge drinking among young people: An application of the theory of planned behaviour. Health Education Research, 13 (2), 163–169. https://doi.org/10.1093/her/13.2.163-a

Norman, P., Cameron, D., Epton, T., Webb, T. L., Harris, P. R., Millings, A., & Sheeran, P. (2018). A randomized controlled trial of a brief online intervention to reduce alcohol consumption in new university students: Combining self-affirmation, theory of planned behaviour messages, and implementation intentions. British Journal of Health Psychology, 23 (1), 108–127. https://doi.org/10.1111/bjhp.12277

Norman, P., & Conner, M. (2006). The theory of planned behaviour and binge drinking: Assessing the moderating role of past behaviour within the theory of planned behaviour. British Journal of Health Psychology, 11 (1), 55–70. https://doi.org/10.1348/135910705X43741

Oei, T. P. S., & Baldwin, A. R. (1994). Expectancy theory: A two-process model of alcohol use and abuse. Journal of Studies on Alcohol, 55 (5), 525–534. https://doi.org/10.15288/jsa.1994.55.525

Oei, T. P. S., & Burrow, T. (2000). Alcohol expectancy and drinking refusal self-efficacy: A test of specificity theory. Addictive Behaviors, 25 (4), 499–507. https://doi.org/10.1016/s0306-4603(99)00044-1

Oei, T. P. S., & Jardim, C. L. (2007). Alcohol expectancies, drinking refusal self-efficacy and drinking behaviour in Asian and Australian students. Drug and Alcohol Dependence, 87 (2–3), 281–287. https://doi.org/10.1016/j.drugalcdep.2006.08.019

Oei, T. P. S., & Morawska, A. (2004). A cognitive model of binge drinking: The influence of alcohol expectancies and drinking refusal self-efficacy. Addictive Behaviors, 29 (1), 159–179. https://doi.org/10.1016/S0306-4603(03)00076-5

Oh, H., & Kim, Y. (2014). Drinking behavior and drinking refusal self-efficacy in Korean college students. Psychological Reports, 115 (3), 872–883. https://doi.org/10.2466/21.18.PR0.115c31z2

Radtke, T., Ostergaard, M., Cooke, R., & Scholz, U. (2017). Web-based alcohol intervention: Study of systematic attrition of heavy drinkers. Journal of Medical Internet Research, 19 (6), e217. https://doi.org/10.2196/jmir.6780

Article   PubMed   PubMed Central   Google Scholar  

Schlegel, R. P., D’Avernas, J. R., Zanna, M. P., DeCourville, N. H., & Manske, S. R. (1992). Problem drinking: A problem for the theory of reasoned action? Journal of Applied Social Psychology, 22 (5), 358–385. https://doi.org/10.1111/j.1559-1816.1992.tb01545.x

Urbán, R., Kökönyei, G., & Demetrovics, Z. (2008). Alcohol outcome expectancies and drinking motives mediate the association between sensation seeking and alcohol use among adolescents. Addictive Behaviors, 33 (10), 1344–1352. https://doi.org/10.1016/j.addbeh.2008.06.006

Young, R., & Oei, T. P. S. (1990). Drinking Expectancy Profile: A manual . University of Queensland.

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Richard Cooke

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Richard O. de Visser

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Cooke, R. (2021). Psychological Theories of Alcohol Consumption. In: Cooke, R., Conroy, D., Davies, E.L., Hagger, M.S., de Visser, R.O. (eds) The Palgrave Handbook of Psychological Perspectives on Alcohol Consumption. Palgrave Macmillan, Cham. https://doi.org/10.1007/978-3-030-66941-6_2

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Published : 11 May 2021

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Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

George f. koob.

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA

Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ -aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least partially, the compulsivity of alcoholism.

1 Definitions and Conceptual Framework for Reward Deficit in Alcoholism

Alcoholism has many definitions that vary from social frameworks to a psychiatric framework embedded in the diagnosis of Substance Dependence on Alcohol defined in the Diagnostic and Statistical Manual of the American Psychiatric Association, 4th edition (DSM-IV; American Psychiatric Association 1994 ). Alcoholism, and more generically drug addiction, can be defined as a chronically relapsing disorder characterized by (i) compulsion to seek and take the drug (alcohol), (ii) loss of control in limiting (alcohol) intake, and (iii) emergence of a negative emotional state (e.g., dysphoria, anxiety and irritability) reflecting a motivational withdrawal syndrome when access to the drug (alcohol) is prevented (defined here as dependence: Koob and Le Moal 1997 ). Clinically and in animal models, the occasional but limited use of alcohol with the potential for abuse or dependence is distinct from escalated alcohol intake and the emergence of a chronic alcohol-dependent state. The thesis argued in the present synthesis is that alcoholism, similar to drug addiction, is a reward deficit disorder, and the “emergence of a negative emotional state” plays an important role in defining and perpetuating alcoholism. Alcoholism also involves substantial neuroadaptations that persist beyond acute withdrawal and trigger relapse and deficits in cognitive function that can also fuel compulsive drinking. However, the argument here is that the core deficit that sets up vulnerability to relapse in alcoholism, and possibly even deficits in cognitive function, is in fact decreased reward function.

To support this hypothesis, a holistic view of alcoholism will be presented with the following arguments. A negative emotional state is a common presentation in most alcoholics during withdrawal and protracted abstinence. Compulsivity observed in alcoholism has an important negative reinforcement component that perpetuates alcoholism. Such negative emotional states become sensitized over time and set up an allostatic state that perpetuates dependence. Negative emotional states set up a powerful motivational state for relapse. Finally, the neurobiological substrates underlying the motivation to seek alcohol will be reviewed, and an argument will be presented that it is loss of reward function and gain of brain stress function that mediate the negative emotional state outlined as key to alcoholism.

Drug addiction has generally been conceptualized as a disorder that involves elements of both impulsivity and compulsivity, in which impulsivity can be defined behaviorally as “a predisposition toward rapid, unplanned reactions to internal and external stimuli without regard for the negative consequences of these reactions to themselves or others” ( Moeller et al. 2001 ). Impulsivity is measured in two domains: the choice of a smaller, immediate reward over a larger, delayed reward ( Rachlin and Green 1972 ) or the inability to inhibit behavior by changing the course of action or to stop a response once it is initiated ( Logan et al. 1997 ). Impulsivity is a core deficit in substance abuse disorders ( Allen et al. 1998 ) and neuropsychiatric disorders such as attention deficit hyperactivity disorder. Operationally, delay-to-gratification tasks (delayed discounting tasks; impulsive choice) and the stop-signal or go/no-go task (behavioral impulsivity) have been used as measures of impulsivity ( Fillmore and Rush 2002 ; Green et al. 1994 ). Compulsivity can be defined as elements of behavior that result in perseveration of responding in the face of adverse consequences or perseveration in the face of incorrect responses in choice situations (e.g., operationally, responding for a drug or alcohol in the face of adverse consequences ( Wolffgramm and Heyne 1995 ) or responding for a drug or alcohol on a progressive-ratio schedule of reinforcement ( Walker et al. 2008 )). Compulsivity is analogous to the symptoms of Substance Dependence outlined by the American Psychiatric Association: continued substance use despite knowledge of having had a persistent or recurrent physical or psychological problem and a great deal of time spent in activities necessary to obtain the substance ( American Psychiatric Association 2000 ).

Collapsing the cycles of impulsivity and compulsivity yields a composite addiction cycle comprising three stages— preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect —in which impulsivity often dominates at the early stages and compulsivity dominates at terminal stages ( Fig. 1 ). As an individual moves from impulsivity to compulsivity, a shift occurs from positive reinforcement driving the motivated behavior to negative reinforcement driving the motivated behavior ( Koob 2004 ). Negative reinforcement can be defined as the process by which removal of an aversive stimulus (e.g., negative emotional state of drug withdrawal) increases the probability of a response (e.g., dependence-induced drug intake to relieve the negative emotional state). Note that negative reinforcement is not punishment, although both involve an aversive stimulus. In punishment, the aversive stimulus suppresses behavior, including drug taking (e.g., disulfiram [Antabuse]). Negative reinforcement can be perhaps described in lay terms as reward via relief (i.e., relief reward), such as removal of pain or in the case of alcoholism removal of the negative emotional state of acute withdrawal or protracted abstinence. The three stages are conceptualized as interacting with each other, becoming more intense, and ultimately leading to the pathological state known as addiction ( Koob and Le Moal 1997 ) ( Fig. 1 ).

(Top left) Diagram showing the stages of impulse control disorder and compulsive disorder cycles related to the sources of reinforcement. In impulse control disorders, an increasing tension and arousal occurs before the impulsive act, with pleasure, gratification, or relief during the act. Following the act, there may or may not be regret or guilt. In compulsive disorders, there are recurrent and persistent thoughts (obsessions) that cause marked anxiety and stress followed by repetitive behaviors (compulsions) that are aimed at preventing or reducing distress ( American Psychiatric Association 1994 ). Positive reinforcement (pleasure/gratification) is more closely associated with impulse control disorders. Negative reinforcement (relief of anxiety or relief of stress) is more closely associated with compulsive disorders. (Top right) Collapsing the cycles of impulsivity and compulsivity results in the addiction cycle, conceptualized as three major components: preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect (Taken with permission from Koob 2008b .) (Bottom) Change in the relative contribution of positive and negative reinforcement constructs during the development of substance dependence on alcohol

In alcohol addiction, or alcoholism, a pattern of oral drug taking evolves that is often characterized by binges of alcohol intake that can be daily episodes or prolonged days of heavy drinking and is characterized by a severe emotional and somatic withdrawal syndrome. Many alcoholics continue with such a binge/withdrawal pattern for extended periods of time, but some individuals can evolve into an opioid-like situation in which they must have alcohol available at all times to avoid the negative consequences of abstinence. Here, intense preoccupation with obtaining alcohol (craving) develops that is linked not only to stimuli associated with obtaining the drug but also to stimuli associated with withdrawal and the aversive motivational state. A pattern develops in which the drug must be obtained to avoid the severe dysphoria and discomfort of abstinence.

The pattern of alcohol addiction, related to reward dysfunction, can be amply illustrated by excerpts from two case histories from Knapp (1996) and Goodwin (1981) . In the first representative case history, an individual progresses from the state where they stated, “I drank when I was happy and I drank when I was anxious and I drank when I was bored and I drank when I was depressed, which was often,” to, “I loved the way drink made me feel, and I loved its special power of deflection, its ability to shift my focus away from my own awareness of self and onto something else, something less painful than my own feelings,” and, “There’s a sense of deep need, and the response is a grabbiness, a compulsion to latch on to something outside yourself in order to assuage some deep discomfort” ( Knapp 1996 ). Similarly, in a second representative case history, “Alcohol seemed to satisfy some specific need I had, which I can’t describe,” and, “There were always reasons to drink. I was low, tense, tired, mad, happy,” and, “The goal, always, was to maintain a glow, not enough, I hoped, that people would notice, but a glow,” and, “By now I was hooked and knew it, but desperately did not want others to know it. I had been sneaking drinks for years—slipping out to the kitchen during parties and such—but now I began hiding alcohol, in my desk, bedroom, car glove compartment, so it would never be far away, ever. I grew panicky even thinking I might not have alcohol when I needed it, which was just about always, “ and, “ I loathed myself. I was waking early and thinking what a mess I was, how I had hurt so many others and myself. The words ‘guilty’ and ‘depression’ sound superficial in trying to describe how I felt. The loathing was almost physical—a dead weight that could be lifted in only one way, and that was by having a drink” ( Goodwin 1981 ; see Koob and Le Moal 2006 , Appendix, for full quotations).

These case histories illustrate numerous key points regarding the present treatise, but the main point to be further discussed below is the transition from drinking to feel good to drinking to avoid feeling bad. To some extent, this transition is facilitated by personality differences, presumably shaped not only by genetics but also by developmental and even social factors. As Khantzian (1997) cogently argued, addiction can be considered a type of chronic emotional distress syndrome that varies with the individual from physical and emotional pain to chronic dysphoria to stress and anxiety to interpersonal difficulties for which drugs can be argued to be sources of self-medication for such negative emotional states. Additionally, he argued that self-medication may be drug-specific—patients may have a preferential use of drugs that fits with the nature of the painful feeling states that they are self-medicating (e.g., opiates to counter intense anger and rage, stimulants as augmenting agents for high-energy individuals, energizing agents for low-energy individuals, and depressants [e.g., alcohol] for individuals who are tense and anxious). The common element argued by Khantzian is that each class of drugs serves as antidotes or correctives to dysphoric states and acts as a “replacement for a defect in the psychological structure” ( Kohut 1971 , p. 46) of such individuals ( Khantzian 2003 ).

1.1 Theoretical Framework: Motivation, Withdrawal, and Opponent Process

Motivation is a state that can be defined as a “tendency of the whole animal to produce organized activity” ( Hebb 1972 ), and such motivational states are not constant but rather vary over time. Early work by Wikler stressed the role of changes in drive states associated with dependence. Subjects described changes in withdrawal as a “hunger” or primary need and the effects of morphine on such a state as “satiation” or gratification of the primary need ( Wikler 1952 ). Although Wikler argued that positive reinforcement was retained even in heavily dependent subjects (thrill of the intravenous opioid injection), dependence produced a new source of gratification, that of negative reinforcement (see above).

The concept of motivation in addiction was inextricably linked with hedonic, affective, or emotional states in the context of temporal dynamics by Solomon’s opponent process theory of motivation. Solomon and Corbit (1974) postulated that hedonic, affective, or emotional states, once initiated by drugs, are automatically modulated by the central nervous system with mechanisms that reduce the intensity of hedonic feelings. The a-process includes affective or hedonic habituation (or tolerance), and the b-process includes affective or hedonic withdrawal (abstinence). The a-process in drug use consists of positive hedonic responses, occurs shortly after presentation of a stimulus, correlates closely with the intensity, quality, and duration of the reinforcer, and shows tolerance. In contrast, the b-process in drug use appears after the a-process has terminated, consists of negative hedonic responses, and is sluggish in onset, slow to build up to an asymptote, slow to decay, and gets larger with repeated exposure. The thesis here is that opponent processes begin early in drug taking, reflect changes in the brain reward and stress systems, and later form one of the major motivations for compulsivity in drug taking.

Thus, dependence or manifestation of a withdrawal syndrome after removal of chronic drug administration is defined in terms of motivational aspects of dependence, such as emergence of a negative emotional state (e.g., dysphoria, anxiety and irritability) when access to the drug is prevented ( Koob and Le Moal 2001 ), rather than on the physical , signs of dependence. Indeed, some have argued that the development of such a negative affective state can define dependence as it relates to addiction:

The notion of dependence on a drug, object, role, activity or any other stimulus-source requires the crucial feature of negative affect experienced in its absence. The degree of dependence can be equated with the amount of this negative affect, which may range from mild discomfort to extreme distress, or it may be equated with the amount of difficulty or effort required to do without the drug, object, etc ( Russell 1976 ).

Alcoholics show dramatic evidence of dysphoric states during acute withdrawal that persist into protracted abstinence. Alcohol withdrawal in humans produces well documented physical (somatic) symptoms, such as tremor, autonomic hyperactivity, nausea, vomiting, and seizures, but more importantly produces significant affective symptoms of anxiety, dysphoria, and depression-like symptoms. Acute withdrawal (i.e., the first week post-alcohol) is characterized by Beck Depression Inventory scores of approximately 20, which is categorized within the range of moderate depression ( Potokar et al. 21997 ; 15–30), and Hamilton Depression Scores of 18, which is close to 20 (the cutoff for antidepressant medication in affective disorder; Brown and Schuckit 1988 ). Depression scores decline during subsequent weeks of treatment but remain at close to 10 for Hamilton Depression Scores for up to 4 weeks of an inpatient treatment program ( Brown and Schuckit 1988 ). In another study of inpatient alcoholics during withdrawal, the Beck Depression Inventory score was at 15 at withdrawal and remained at 12.8 two days into withdrawal and at 9.4 two weeks post-withdrawal ( de Timary et al. 2008 ). Similar results were obtained for anxiety measures ( Potokar et al. 1997 ; de Timary et al. 2008 ). In another study with a long-term follow-up of 6 months after a 4-week inpatient detoxification. Beck Depression Inventory scores remained at approximately 6, and trait anxiety scores (STAI-X2) remained above 33 even in subjects without comorbid anxiety or depression ( Driessen et al. 2001 ). Independent of comorbidity status, individuals who relapsed had higher trait anxiety scores than those who abstained ( Driessen et al. 2001 ). Thus, although alcoholics show significant decreases in measures of depression and anxiety during withdrawal, there is a measurable level of depression-like symptoms that persist long after acute withdrawal into protracted abstinence that may be clinically (treatment) relevant.

More compelling for the present thesis, during a 2-week inpatient withdrawal study, alexithymia (defined as a state of deficiency in understanding, processing, or describing emotions: from the Greek a for “lack.” lexis for “word,” and thymos for “emotion”; Sifneos 1973 ; Taylor and Bagby 2000 ), which results in poor emotional regulation and stress management abilities, remained high and stable during the 2-week period ( de Timary et al. 2008 ). Alexithymia scores did not decline between the 0 and 2 day time-points but remained high at a score of 57 and declined only to 53 at the 3-week time-point ( de Timary et al. 2008 ). The authors argued that alexithymia is a stable personality trait in alcoholics rather than a state-dependent phenomenon, providing support for the self-medication hypothesis outlined above.

Animal models can also be used to test the hypothesis that there are opponent process-like motivational changes associated with the development of alcohol dependence. Electrical brain stimulation reward or intracranial self-stimulation has a long history as a measure of activity of the brain reward system and of the acute reinforcing effects of drugs of abuse. All drugs of abuse, when administered acutely, decrease brain stimulation reward thresholds ( Kornetsky and Esposito 1979 ) and when administered chronically increase reward thresholds during withdrawal (see above). Brain stimulation reward involves widespread neurocircuitry in the brain, but the most sensitive sites defined by the lowest thresholds involve the trajectory of the medial forebrain bundle that connects the ventral tegmental area with the basal forebrain ( Olds and Milner 1954 ; Koob et al. 1977 ). Although much emphasis was focussed initially on the role of the ascending monoamine systems in the medial forebrain bundle in brain stimulation reward, other nondopaminergic systems in the medial forebrain bundle clearly play a key role ( Hernandez et al. 2006 ).

Rats made dependent using chronic ethanol vapor exposure at blood alcohol levels sufficient to drive excessive drinking showed an increase in brain reward thresholds during withdrawal that lasted up to 3 days post-withdrawal ( Schulteis et al. 1995 ). However, data suggest that, similar to other drugs of abuse, such opponent-like processes can begin with a single dosing ( Fig. 2 ).

a Withdrawal from a single boul of acute ethanol intoxication (week 1) resulted in a significant but transient increase in brain reward threshold only with the highest dose of ethanol tested (2.0 g/kg: a P < 0.05, compared with vehicle controls at given time-point post-injection). The effect was significant at 6 hours, a time when blood alcohol levels had declined to virtually undetectable levels following this dose of ethanol. Repeated treatment with this dose for two additional weeks resulted in a progressive broadening of the duration of significant threshold elevations. By comparison, treatment with 1.5 g/kg ethanol resulted in significant but transient elevations only after three repeated bouts of intoxication/withdrawal, and no statistically reliable changes were seen after one or two treatments (data not shown). Treatment with 1.0 g/kg did not produce any statistically reliable threshold changes regardless of treatment week (data not shown). Data are expressed as mean ± SEM percentage of baseline threshold, n = 8–10 per dose group. [Taken with permission from Schulteis and Liu 2006 .] b Time-dependent elevation of intracranial self-stimulation thresholds during ethanol withdrawal. Mean blood alcohol levels were 197.29 mg%, Data are expressed as mean ± SEM percentage of baseline threshold, a p < 0.05, thresholds that were significantly elevated above control levels at 2–48 hours post-ethanol. Open circles indicate the control condition. Closed circles indicate the ethanol withdrawal condition. [Taken with permission from Schulteis et al. 1995 .]

An acute elevation in brain reward thresholds was observed during repeated acute withdrawal from ethanol, bearing a striking resemblance to human subjective reports ( Schulteis and Liu 2006 ) ( Fig. 2 ). These results demonstrate that the elevation in brain reward thresholds following prolonged access to alcohol may fail to return to baseline levels between repeated and prolonged exposure to alcohol self-administration (i.e., a residual reward deficit), thus creating the greater elevation in reward thresholds observed during withdrawal from chronic ethanol. Rapid acute tolerance and opponent process-like effects in response to the hedonic effects of alcohol have been reported in human studies using the alcohol clamp procedure ( Morzorati et al. 2002 ). These data provide compelling evidence for brain reward dysfunction with chronic alcohol, which provides strong support for a hedonic allostasis model of alcoholism ( Koob 2003 ).

The dysregulation of brain reward function associated with withdrawal from chronic administration of drugs of abuse is a common element of all drugs of abuse. Withdrawal from chronic cocaine ( Markou and Koob 1991 ), amphetamine ( Paterson et al. 2000 ), opioids ( Schulteis et al. 1994 ), cannabinoids ( Gardner and Vorel 1998 ), nicotine ( Epping-Jordan et al. 1998 ), and ethanol ( Schulteis et al. 1995 ) leads to increases in reward thresholds during acute abstinence, and some of these elevations in threshold can last for up to 1 week. These observations lend credence to the hypothesis that opponent processes can set the stage for one aspect of compulsivity in which negative reinforcement mechanisms are engaged.

More recently, the opponent process theory has been expanded into the domains of the neurobiology of drug addiction from a neurocircuitry perspective. An allostatic model of the brain motivational systems has been proposed to explain the persistent changes in motivation that are associated with dependence in addiction ( Koob and Le Moal 2001 , 2008 ). In this formulation, addiction is conceptualized as a cycle of increasing dysregulation of brain reward/anti-reward mechanisms that results in a negative emotional state contributing to the compulsive use of drugs. Counteradaptive processes that are part of the normal homeostatic limitation of reward function fail to return within the normal homeostatic range. These counteradaptive processes are hypothesized to be mediated by two mechanisms: within-system neuroadaptations and between-system neuroadaptations ( Koob and Bloom 1988 ).

In a within-system neuroadaptation. “the primary cellular response element to the drug would itself adapt to neutralize the drug’s effects: persistence of the opposing effects after the drug disappears would produce the withdrawal response” ( Koob and Bloom 1988 ). Thus, a within-system neuroadaptation is a molecular or cellular change within a given reward circuit to accommodate overactivity of hedonic processing associated with addiction resulting in a decrease in reward function.

The emotional dysregulation associated with the withdrawal/negative affect stage may also involve between-system neuroadaptations in which neurochemical systems other than those involved in the positive rewarding effects of drugs of abuse are recruited or dysregulated by chronic activation of the reward system. “In the between-systems opposing process, a different cellular system and separable molecular apparatus would be triggered by the changes in the primary drug response neurons and would produce the adaptation and tolerance” ( Koob and Bloom 1988 ). Thus, a between-system neuroadaptation is a circuitry change in which another different circuit (anti-reward circuit) is activated by the reward circuit and has opposing actions, again limiting reward function. The remainder of this review explores the neuroadaptational changes that occur in the brain emotional systems to account for the neurocircuitry changes that produce opponent processes and are hypothesized to play a key role in the compulsivity of addiction.

2 Animal Models for Compulsive Alcohol Seeking

Methods of inducing binge-like drinking with alcohol range from having animals drink alcohol solutions that are made more palatable with the addition of a sweetener ( Ji et al. 2008 ) to restricting intake to specific periods of the dark cycle (drinking in the dark; Rhodes et al. 2005 ) to models involving alcohol dependence in animals such as alcohol vapor inhalation, intragastric alcohol infusion, and alcohol-liquid diet. The compulsive use of alcohol derives from multiple sources of reinforcement, and animal models have been developed not only for the acute positive reinforcing effects of ethanol, but also for the negative reinforcing effects associated with removal of the aversive effects of ethanol withdrawal or an existing aversive state (i.e., self-medication of the aversive effects of abstinence from chronic ethanol or self-medication of a pre-existing negative affective state; Koob and Le Moal 1997 ). A major early breakthrough was the development of a training procedure involving access to a sweetened solution and a subsequent fading in of ethanol to avoid the aversiveness of the ethanol taste (for review, see Samson 1987 ). Subsequent work extended these procedures to measures of self-administration in dependent rats and post-dependent rats ( Roberts et al. 1996 ; O’Dell et al. 2004 ).

High doses of alcohol solution will be self-administered intragastrically after animals are made dependent via passive intragastric infusion, and rats will self-infuse 4–7 g/kg per day of ethanol ( Fidler et al. 2006 ). Here, blood alcohol levels average 0.12 g%, measured 30 min after the start of a bout in which rats infuse 1.5 g/kg per 30 min.

In an alcohol-liquid diet procedure, the diet is typically the sole source of calories available to rats (for example, see Moy et al. 1997 ), thereby forcing rats to consume the alcohol. Typically, rats are provided a palatable liquid diet containing 5–8.7% v/v ethanol as their sole source of calories sufficient to produce dependence and maintain blood alcohol levels of 100–130 mg% during the dark (active drinking) cycle ( Schulteis et al. 1996 ; Brown et al. 1998 ; Valdez et al. 2004). High responders during withdrawal from liquid diet will reach blood alcohol levels of approximately 80–100 mg% ( Schulteis et al. 1996 ; Gilpin et al. 2009 ).

Reliable self-administration of ethanol in dependent animals using ethanol vapor exposure has been extensively characterized in rats, in which animals obtain blood alcohol levels in the 100–150 mg% range ( Roberts et al. 1999 , 2000 ). Similarly, rats with a history of alcohol dependence show increased self-administration of ethanol, even weeks after acute withdrawal ( Roberts et al. 2000 ). In a variant of alcohol vapor exposure with more face validity, intermittent exposure to chronic ethanol using alcohol vapor chambers (14 h on/10 h off) produces more rapid escalation to increased ethanol intake and higher amounts of intake ( O’Dell et al. 2004 ; Rimondini et al. 2002 ), and blood alcohol levels are reliably above 140 mg% after a 30 min session of self-administration in dependent animals ( Richardson et al. 2008 ). In both the liquid diet and ethanol vapor procedures, alcohol intake is directly related to the blood alcohol range and the pattern of intermittent high-dose alcohol exposure ( Gilpin et al. 2009 ). Although the alcohol vapor model may have limited face validity, considering that alcohol is passively administered to animals, numerous studies demonstrated that it also has robust predictive validity for alcohol addiction ( Heilig and Koob 2007 ; Koob et al. 2009 ).

A similar procedure has been developed for mice and produces reliable increases in ethanol self-administration during withdrawal. Now termed chronic intermittent exposure (CIE), C57BL/6 mice are exposed to intermittent durations of ethanol vapor (three cycles of 16 h of vapor and 8 h of air) and then tested in a 2 h limited access ethanol preference drinking test during the circadian dark period ( Becker and Lopez 2004 ; Lopez and Becker 2005 ; Finn et al. 2007 ). Intermittent ethanol vapor exposure significantly increased 15% (v/v) ethanol intake by 30–50% in the post-vapor period, usually after multiple cycles and usually after 24 h of withdrawal ( Finn et al. 2007 ). Similar results have been reported using an operant response in mice in 60 min test sessions for 10% (w/v) ethanol with intermittent vapor exposure of 14 h on/10 h off ( Chu et al. 2007 ).

3 Neural Substrates for the Negative Emotional State Associated with Alcoholism

3.1 within-system neuroadaptations that contribute to the compulsivity associated with the dark side of alcoholism.

Within-system neuroadaptations to chronic drug exposure include decreases in function of the same neurotransmitter systems in the same neurocircuits implicated in the acute reinforcing effects of drugs of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal and protracted abstinence. This decrease in dopamine function is hypothesized to lead to decreased motivation for non-drug-related stimuli and increased sensitivity to the abused drug ( Melis et al. 2005 ). Activation of the mesolimbic dopamine system has long been known to be critical for the acute rewarding properties of psychostimulant drugs and to be associated with the acute reinforcing effects of alcohol ( Koob 1992 ; McBride and Li 1998 ; Nestler 2005 ). However, the magnitude of the increase in dopaminergic activity produced by alcohol pales in comparison to that of psychostimulant “intoxication.” For example, intravenous cocaine self-administration produces a 200% increase in extracellular dopamine ( Weiss et al. 1992b ) compared with ethanol which produces a 20% increase in extracellular dopamine in the nucleus accumbens ( Doyon et al. 2003 ) and heroin (which does not increase extracellular dopamine in the nucleus accumbens) ( Table 1 ). Such a relationship changes with the development of dependence and may change with genetic background (see Ramachandani et al. 2010 , who demonstrated a nearly 200% increase with alcohol in animals that carried the OPRM1 118G variant).

Effects of intravenous self-administration of D-amphetamine, cocaine, and heroin and oral self-administration of alcohol on extracellular dopamine levels in the nucleus accumbens using in vivo microdialysis

More compelling in the mesolimbic dopamine domain are the decreases in activity of the mesolimbic dopamine system and decreases in serotonergic neurotransmission in the nucleus accumbens that occur during alcohol withdrawal in animal studies ( Rossetti et al. 1992 ; Weiss et al. 1992a , 1996 ). In dependent male Wistar rats trained to self-administer ethanol during withdrawal, the release of dopamine and serotonin was monitored by microdialysis in the nucleus accumbens at the end of a 3–5 week ethanol (8.7% w/v) liquid diet regimen, during 8 h of withdrawal, and during renewed availability of ethanol involving the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by unlimited access to the ethanol liquid diet. In nondependent rats, operant ethanol self-administration increased both dopamine and serotonin release in the nucleus accumbens. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 h withdrawal period. Self-administration of ethanol reinstated and maintained dopamine release at pre-withdrawal levels but failed to completely restore serotonin efflux. These findings suggested that deficits in nucleus accumbens monoamine release may contribute to the negative affective consequences of ethanol withdrawal and thereby motivate ethanol-seeking behavior in dependent subjects ( Weiss et al. 1996 ). Similar dramatic decreases in extracellular dopamine in the nucleus accumbens, measured by microdialysis, were found in a study in which animals were tested for 8 h into ethanol withdrawal produced by chronic repeated ethanol injections of up to 5 g/kg every 6 h for six consecutive days using the Majchrowicz procedure ( Majchrowicz 1975 ; Rossetti et al. 1999 ). Thus, as a result, ethanol-dependent animals may show a much greater percentage increase in dopamine release in the nucleus accumbens during ethanol self-administration during withdrawal because baseline levels of dopamine are so low during withdrawal ( Weiss et al. 1996 ).

Imaging studies in drug-addicted humans have consistently shown long-lasting decreases in the numbers of dopamine D 2 receptors in alcoholics compared with controls ( Volkow et al. 2002 ). Additionally, alcohol-dependent subjects had dramatically reduced dopamine release in the striatum response to a pharmacological challenge with the stimulant drug methylphenidate ( Volkow et al. 2007 ). Decreases in the number of dopamine D 2 receptors, coupled with the decrease in dopaminergic activity, in cocaine, nicotine, and alcohol abusers are hypothesized to produce a decreased sensitivity of reward circuits to stimulation by natural rein-forcers ( Martin-Solch et al. 2001 ; Volkow and Fowler 2000 ). These findings suggest an overall reduction in the sensitivity of the dopamine component of reward circuitry to natural reinforcers and other drugs in drug-addicted individuals ( Table 2 ).

Role of corticotropin-releasing factor in dependence

nt, not tested

CeA, central nucleus of the amygdala

Other within-system neuroadaptations under this conceptual framework could include increased sensitivity of receptor transduction mechanisms in the nucleus accumbens. Drugs of abuse have acute receptor actions that are linked to intracellular signaling pathways that may undergo adaptations with chronic treatment. In the context of chronic alcohol administration, multiple molecular mechanisms have been hypothesized to counteract the acute effects of ethanol that could be considered within-system neuroadaptations. For example, chronic ethanol decreases γ -aminobutyric acid (GABA) receptor function, possibly through downregulation of the α 1 subunit ( Mhatre et al. 1993 ; Devaud et al. 1997 ). Chronic ethanol also decreases the acute inhibition of adenosine reuptake (i.e., tolerance develops to the inhibition of adenosine by ethanol; Sapru et al. 1994 ). Perhaps more relevant to the present treatise, whereas acute ethanol activates adenylate cyclase, withdrawal from chronic ethanol decreases CREB phosphorylation in the amygdala and is linked to decrease in function of neuropeptide Y (NPY) and to the anxiety-like responses observed during acute ethanol withdrawal ( Chance et al. 2000 ; Pandey 2004 ).

3.2 Between-System Neuroadaptations that Contribute to Compulsivity Associated with the Dark Side of Alcoholism

Brain neurochemical systems involved in arousal-stress modulation may also be engaged within the neurocircuitry of the brain stress systems in an attempt to overcome the chronic presence of the perturbing drug (alcohol) and to restore normal function despite the presence of drug. The neuroanatomical entity termed the extended amygdala ( Heimer and Alheid 1991 ) may represent a common anatomical substrate integrating brain arousal-stress systems with hedonic processing systems to produce some of the between-system opponent process elaborated above. The extended amygdala is composed of the central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition zone in the medial (shell) subregion of the nucleus accumbens. Each of these regions has cytoarchitectural and circuitry similarities ( Heimer and Alheid 1991 ). The extended amygdala receives numerous afferents from limbic structures, such as the basolateral amygdala and hippocampus, and sends efferents to the medial part of the ventral pallidum and a large projection to the lateral hypothalamus, thus further defining the specific brain areas that interface classical limbic (emotional) structures with the extrapyramidal motor system ( Alheid et al. 1995 ). The extended amygdala has long been hypothesized to play a key role not only in fear conditioning ( Le Doux 2000 ) but also in the emotional component of pain processing ( Neugebauer et al. 2004 ).

The brain stress system mediated by corticotropin-releasing factor (CRF) systems in both the extended amygdala and hypothalamic–pituitary–adrenal axis are dysregulated by chronic administration of all major drugs with dependence or abuse potential, with a common response of elevated adrenocorticotropic hormone, corticosterone, and extended amygdala CRF during acute withdrawal from chronic drug administration ( Rivier et al. 1984 ; Merlo-Pich et al. 1995 ; Koob et al 1994 ; Rasmussen et al. 2000 ; Olive et al. 2002 ; Delfs et al. 2000 ; Koob 2008a ).

More specifically, alcohol withdrawal reliably produces anxiety-like responses in animal models that can be reversed by CRF receptor antagonists ( Koob 2008a ). Ethanol withdrawal produces anxiety-like behavior that is reversed by intracerebroventricular administration of CRF 1 /CRF 2 peptidergic antagonists ( Baldwin et al. 1991 ), small-molecule CRF 1 antagonists ( Knapp et al. 2004 ; Overstreet et al. 2004 ; Funk et al. 2007 ), and intracerebral administration of a peptidergic CRF 1 /CRF 2 antagonist into the amygdala ( Rassnick et al. 1993 ). CRF antagonists injected intracerebroventricularly or systemically also block the potentiated anxiety-like responses to stressors observed during protracted abstinence from chronic ethanol ( Breese et al. 2005 ; Valdez et al. 2003 ; Sommer et al. 2008 ).

Perhaps more relevant to the present thesis are studies showing that intermittent alcohol exposure sensitizes withdrawal of anxiety-like responses and that administration of drug treatments during withdrawal from the first and second alcohol cycles blocked this sensitization of withdrawal ( Knapp et al. 2004 ). Diazepam, flumazenil (a GABA A receptor partial agonist), and baclofen (a GABA B receptor agonist) blocked the sensitization of withdrawal, consistent with a within-system neuroadaptation ( Knapp et al. 2004 , 2005 , 2007 ; see above). However, a CRF 1 , antagonist also prevented the sensitization of withdrawal-induced anxiety ( Overstreet et al. 2004a . 2005 ). These results are consistent with a prolonged history of alcohol exposure producing persistent upregulation of both CRF and CRF 1 , receptors in the brain ( Roberto et al. 2010 ; Sommer et al. 2008 ; Zorrilla et al. 2001 ).

The ability of CRF antagonists to block the anxiogenic-like and aversive-like motivational effects of drug withdrawal would predict motivational effects of CRF antagonists in animal models of extended access to drugs. A particularly dramatic example of the motivational effects of CRF in dependence can be observed in animal models of ethanol self-administration in dependent animals. During ethanol withdrawal, extrahypothalamic CRF systems become hyperactive, with an increase in extracellular CRF within the central nucleus of the amygdala and bed nucleus of the stria terminalis in dependent rats ( Funk et al. 2006 ; Merlo-Pich et al. 1995 ; Olive et al. 2002 ). The dysregulation of brain CRF systems is hypothesized to underlie not only the enhanced anxiety-like behaviors but also the enhanced ethanol self-administration associated with ethanol withdrawal. Supporting this hypothesis, the subtype nonselective CRF receptor antagonists α -helical CRF 9–41 and D-Phe CRF 12–41 (intracerebroventricular administration) reduced ethanol self-administration in dependent animals during acute withdrawal and during protracted abstinence ( Valdez et al. 2002 ). When administered directly into the central nucleus of the amygdala, a CRF 1 /CRF 2 antagonist blocked ethanol self-administration in ethanol-dependent rats ( Funk et al. 2006 ). Systemic injections of small-molecule CRF 1 , antagonists also blocked the increased ethanol intake associated with acute withdrawal and protracted abstinence ( Gehlert et al. 2007 ; Funk et al. 2007 ). These data suggest an important role for CRF, primarily within the central nucleus of the amygdala, in mediating the increased self-administration associated with dependence. Consistent with the sensitization of the withdrawal response associated with repeated alcohol exposure, a CRF antagonist administered during repeated withdrawal also blocked the development of excessive drinking during withdrawal ( Roberto et al. 2010 ).

Although less well developed, evidence supports a role of norepinephrine systems in the extended amygdala in the negative motivational state and increased self-administration associated with dependence. Substantial evidence has accumulated suggesting that in animals and humans, central noradrenergic systems are activated during acute withdrawal from ethanol. Alcohol withdrawal in humans is associated with activation of noradrenergic function, and the signs and symptoms of alcohol withdrawal in humans are blocked by postsynaptic β -adrenergic blockade ( Romach and Sellers 1991 ). Alcohol withdrawal signs are also blocked in animals by administration of α 1 antagonists and β -adrenergic antagonists and selective blockade of norepinephrine synthesis ( Trzaskowska and Kostowski 1983 ). In dependent rats, the α 1 , antagonist prazosin selectively blocked the increased drinking associated with acute withdrawal ( Walker et al. 2008 ). Thus, converging data suggest that noradrenergic neurotransmission is enhanced during ethanol withdrawal and that noradrenergic functional antagonists can block aspects of ethanol withdrawal.

Dynorphin, an opioid peptide that binds to κ opioid receptors, has long been known to show activation with chronic administration of psychostimulants and opioids ( Nestler 2004 ; Koob 2008a ), and κ opioid receptor agonists produce aversive effects in animals and humans ( Mucha and Herz 1985 ; Pfeiffer et al. 1986 ). Although κ agonists suppress nondependent drinking, possibly via aversive stimulus effects ( Wee and Koob 2010 ), κ opioid antagonists block the excessive drinking associated with ethanol withdrawal and dependence ( Holter et al. 2000 ; Walker and Koob 2008 ). Recently, some have argued that the effects of CRF in producing negative emotional states are mediated by activation of κ opioid systems ( Land et al. 2008 ). However, κ receptor activation can activate CRF systems in the spinal cord ( Song and Takemori 1992 ), and there is pharmacological evidence that dynorphin systems can also activate the CRF system. A CRF 1 , antagonist blocked κ agonist-induced reinstatement of cocaine seeking in squirrel monkeys ( Valdez et al. 2007 ).

The dynamic nature of the brain stress system response to challenge is illustrated by the pronounced interaction of central nervous system CRF systems and central nervous system norepinephrine systems. Conceptualized as a feed-forward system at multiple levels of the pons and basal forebrain. CRF activates norepinephrine, and norepinephrine in turn activates CRF ( Koob 1999 ). Much pharmacologic, physiologic, and anatomic evidence supports an important role for a CRF-norepinephrine interaction in the region of the locus coeruleus in response to stressors ( Valentino et al. 1991 , 1993 ; Van Bockstaele et al. 1998 ). However, norepinephrine also stimulates CRF release in the paraventricular nucleus of the hypothalamus ( Alonso et al. 1986 ), bed nucleus of the stria terminalis, and central nucleus of the amygdala. Such feed-forward systems were further hypothesized to have powerful functional significance for mobilizing an organism’s response to environmental challenge, but such a mechanism may be particularly vulnerable to pathology ( Koob 1999 ).

Neuropeptide Y is a neuropeptide with dramatic anxiolytic-like properties localized to the amygdala and has been hypothesized to have effects opposite to CRF in the negative motivational state of withdrawal from drugs of abuse ( Heilig and Koob 2007 ). Significant evidence suggests that activation of NPY in the central nucleus of the amygdala can block the motivational aspects of dependence associated with chronic ethanol administration. Neuropeptide Y administered intracerebroventricularly blocked the increased drug intake associated with ethanol dependence ( Thorsell et al. 2005a , b ). Injection of NPY directly into the central nucleus of the amygdala ( Gilpin et al. 2008 ) and viral vector-enhanced expression of NPY in the central nucleus of the amygdala also blocked the increased drug intake associated with ethanol dependence ( Thorsell et al. 2007 ).

Thus, acute withdrawal from drugs increases CRF in the central nucleus of the amygdala, which has motivational significance for the anxiety-like effects of acute withdrawal from alcohol and the increased drug intake associated with dependence. Acute withdrawal may also increase the release of norepinephrine in the bed nucleus of the stria terminalis and dynorphin in the nucleus accumbens, both of which may contribute to the negative emotional state associated with dependence. Decreased activity of NPY in the central nucleus of the amygdala may contribute to the anxiety-like state associated with ethanol dependence. Activation of brain stress systems (CRF, norepinephrine and dynorphin) combined with inactivation of brain anti-stress systems (NPY) elicits powerful emotional dysregulation in the extended amygdala. Such dysregulation of emotional processing may be a significant contribution to the between-system opponent processes that help maintain dependence and also set the stage for more prolonged state changes in emotionality such as in protracted abstinence.

4 Compulsivity in Alcoholism: an Allostatic View

Compulsivity in alcoholism can derive from multiple sources, including enhanced incentive salience, engagement of habit function, and impairment in executive function. However, underlying each of these sources is a negative emotional state that may strongly impact on compulsivity. The development of the negative emotional state that drives the negative reinforcement of addiction has been defined as the “dark side” of addiction ( Koob and Le Moal 2005 , 2008 ) and is hypothesized to be the b-process of the hedonic dynamic known as opponent process when the a-process is euphoria. The negative emotional state that comprises the withdrawal/negative affect stage consists of key motivational elements, such as chronic irritability, emotional pain, malaise, dysphoria, alexithymia, and loss of motivation for natural rewards, and is characterized in animals by increase in reward thresholds during withdrawal from all major drugs of abuse. Two processes are hypothesized to form the neurobiological basis for the b-process: loss of function in the reward systems (within-system neuroadaplation) and recruitment of the brain stress or anti-reward systems (between-system neuroadaptation; Koob and Bloom 1988 ; Koob and Le Moal 1997 ). Anti-reward is a construct based on the hypothesis that brain systems are in place to limit reward ( Koob and Le Moal 2008 ). As dependence and withdrawal develop, brain stress systems, such as CRF, norepinephrine, and dynorphin, are recruited, producing aversive or stress-like states ( Koob 2003 ; Nestler 2001 ; Aston-Jones et al. 1999 ). At the same time, within the motivational circuits of the ventral striatum-extended amygdala, reward function decreases. The combination of decreases in reward neurotransmitter function and recruitment of anti-reward systems provides a powerful source of negative reinforcement that contributes to compulsive drug-seeking behavior and addiction ( Fig. 3 ).

Pathways for key elements of addiction circuitry implicated in negative emotional states. Addiction circuitry is composed of structures involved in the three stages of the addiction cycle: binge/intoxication (ventral striatum, dorsal striatum and thalamus), withdrawal/negative affect (ventral striatum, bed nucleus of the stria terminalis and central nucleus of the amygdala), preoccupation/anticipation (prefrontal cortex, orbitofrontal cortex and hippocampus). Highlighted here for the withdrawal/negative affect stage is increased activity in the extended amygdala and decreased activity in the reward system, illustrated with the use of imaging colors (i.e., red for high activity and blue for low activity). Modified with permission from Blackburn-Munro and Blackburn-Munro (2003) and Koob et al. (2008) . AMG, amygdala; BNST, bed nucleus of the stria terminalis; DS, dorsal striatum; GP, globus pallidus; Hippo, hippocampus; Hyp, hypothalamus; Insula, insular cortex; OFC, orbitofrontal cortex; PFC, prefrontal cortex; Thal, thalamus; VS, ventral striatum; and VTA, ventral tegmental area. [Modified with permission from Zald and Kim 2001 ]

An overall conceptual theme argued here is that drug addiction represents a break with homeostatic brain regulatory mechanisms that regulate the emotional state of the animal. The dysregulation of emotion begins with the binge and subsequent acute withdrawal, but leaves a residual neuroadaptive trace that allows rapid “re-addiction” even months and years after detoxification and abstinence. Thus, the emotional dysregulation of alcohol addiction represents more than simply a homeostatic dysregulation of hedonic function—it also represents a dynamic break with homeostasis of this system that has been termed allostasis ( Koob 2003 ).

Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, can be defined simply as “stability through change” ( Sterling and Eyer 1988 ). Allostasis is different from homeostasis. Allostasis involves a feed-forward mechanism rather than the negative feedback mechanisms of homeostasis. Allostasis involves a changed set point with continuous re-evaluation of need and continuous readjustment of all parameters toward new set points. The set point in question here is emotional state. An allostatic state can be defined as a state of chronic deviation of the reward system from its normal (homeostatic) operating level. Allostatic load has been defined as the “long-term cost of allostasis that accumulates over time and reflects the accumulation of damage that can lead to pathological states” ( McEwen 2000 ). Although the concept of allostatic state has not received much attention, the argument here is that alcoholism reflects largely a movement to an allostatic state, often before sufficient pathology has ensued to produced allostatic load sufficient for physical pathology ( Koob and Le Moal 2001 ).

Allostatic mechanisms have been hypothesized to be involved in maintaining a functioning brain reward system that has relevance for the pathology of addiction ( Koob and Le Moal 2001 ). Two components are hypothesized to adjust to challenges of the brain produced by drugs of abuse: underactivation of brain reward transmitters and circuits and recruitment of the brain anti-reward or brain stress systems ( Fig. 4 ). Thus, the very physiological mechanism that allows rapid responses to environmental challenge becomes the source of pathology if adequate time or resources are not available to shut off the response (one example is the interaction between CRF and norepinephrine in the brainstem and basal forebrain that could lead to pathological anxiety; Koob 1999 ).

a Schematic of the progression of alcohol dependence over time, illustrating the shift in underlying motivational mechanisms. From initial, positive reinforcing, pleasurable alcohol effects, the addictive process progresses over time to being maintained by negative reinforcing relief from a negative emotional state. Data presented in this paper suggest that neuroadaptations encompassing the recruitment of extrahypothalamic CRF systems are key to this shift. (Taken with permission from Heilig and Koob 2007 .) b The a-process represents a positive hedonic or positive mood state, and the b-process represents the negative hedonic or negative mood state. The affective stimulus (state) has been argued to be the sum of both the a-process and b-process. An individual who experiences a positive hedonic mood state from a drug of abuse with sufficient time between re-administering the drug is hypothesized to retain the a-process. An appropriate counteradaptive opponent process (b-process) that balances the activational process (a-process) does not lead to an allostatic state. The changes in the affective stimulus (state) in an individual with repeated frequent drug use may represent a transition to an allostatic state in the brain systems and, by extrapolation, a transition to addiction ( see text). Notice that the apparent b-process never returns to the original homeostatic level before drug taking begins again, thus creating a greater and greater allostatic state in the brain emotional systems. The counteradaptive opponent-process (b-process) does not balance the activational process (a-process) but in fact shows a residual hysteresis. Although these changes illustrated in the figure are exaggerated and condensed over time, the hypothesis is that even during post-detoxification (a period of “protracted abstinence”), the brain emotional systems still bear allostatic changes ( see text). The following definitions apply: alkalosis, the process of achieving stability through change; allostatic state, a state of chronic deviation of the regulatory system from its normal (homeostatic) operating level: allostatic load, the cost to the brain and body of the deviation, accumulating over time, and reflecting in many cases pathological states and accumulation of damage. [Modified with permission from Koob and Le Moal 2001 .]

Repeated challenges, such as with repeated alcohol binges, lead to attempts of the brain via molecular, cellular, and neurocircuitry changes to maintain stability but at a cost. For the alcoholism framework elaborated here, the residual deviation from a normal emotional state is termed the allostatic state. This state represents a combination of chronic elevation of the reward set point fueled by decreased function of reward circuits and recruitment of anti-reward systems, both of which lead to the compulsivity of alcohol-seeking and alcohol taking. How these systems are modulated by other known brain emotional systems localized to the basal forebrain, where the ventral striatum and extended amygdala project to convey emotional valence, how the dysregulation of brain emotional systems impacts on the cognitive domain linked to impairments in executive function, and how individuals differ at the molecular-genetic level of analysis to convey loading on these circuits remain challenges for future research ( George and Koob 2010 ).

As such, the present thesis does not preclude a key role for other systems associated with the addiction process, including the mesolimbic dopamine system involved in incentive salience, the dorsal striatum involved in habit formation, the parabrachial amygdala and spinothalamocortical systems involved in pain, and the prefrontal cortex involved in decision-making ( Koob and Volkow 2010 ; George and Koob 2010 ). Such modules are driven by bottom-up signals from both the external world and interoceptive signals and by top-down signals from higher-order systems mediating cognitive control. Indeed, the failure of a specific module may differ from one individual to another and may represent a neuropsychobiological mechanism underlying individual differences in the vulnerability to drug addiction. For example, we have hypothesized that individual differences in the function of the incentive salience mesolimbic dopamine system and the habit/striatum modules may be particularly important for craving-type 1 (or reward craving), defined as craving for the rewarding effects of alcohol and usually induced by stimuli that have been paired with alcohol self-administration, such as environmental cues. Additionally, hypoactivity of the decision-making/prefrontal cortex module may lead to a loss of control over drug intake despite negative consequence because of impaired inhibitory control and decision-making leading to choices of immediate rewards over delayed rewards ( Goldstein and Volkow 2002 ).

Nevertheless the hypothesis outlined here is that a core component of alcoholism involves hyperactivity of the negative emotional state/extended amygdala system that is associated with increased emotional pain and stress and might be a risk factor for drug use as self-medication for emotional pain, dysphoria, and stress ( Khantzian 1997 ). A subhypothesis is that vulnerability in the emotional pain parabrachial-amygdala system ( Besson 1999 ; Shurman et al. 2010 ) may lead to increased emotional pain during withdrawal and intense craving-type 2 (or withdrawal relief craving), which is conceptualized as an excessive motivation for the drug to obtain relief from a state change characterized by anxiety and dysphoria after protracted abstinence ( Heinz et al. 2003 ), thus contributing to the preponderant role of the withdrawal/negative affect stage that characterizes alcoholism. Increased reactivity of the stress/hypothalamic-pituitary-adrenal axis module may be critical in the initiation of alcohol intake and for the maintenance of drug intake which have little initial rewarding value, such as nicotine. Activation of the hypothalamic-pituitary-adrenal axis can potentiate the reinforcing effects of drugs ( Piazza and Le Moal 1998 ). However, this activation can in turn drive amygdala CRF. further exacerbating the development of negative emotional states ( Koob and Kreek 2007 ). Although the initial deficit in a specific functional circuit that drives excessive drinking might be specific to one stage of the addiction cycle, as the transition to addiction progresses, an individual is ultimately likely to show a progressive and generalized loss of control over many, if not all, systems. However, the thesis argued here is that as excessive alcohol intake progresses to Substance Dependence on Alcohol (Alcoholism), a common dysregulated functional element is a reward system deficit.

Acknowledgments

The author would like to thank Michael Arends for assistance with manuscript preparation and editing. Research was supported by National Institutes of Health grants AA06420 and AA08459 from the National Institute on Alcohol Abuse and Alcoholism and the Pearson Center for Alcoholism and Addiction Research. This is publication number 20763 from The Scripps Research Institute.

• Alheid GF, De Olmos JS, Beltramino CA. Amygdala and extended amygdala. In: Paxinos G, editor. The rat nervous system. Academic Press; San Diego: 1995. pp. 495–578. [ Google Scholar ]
• Allen TJ, Moeller FG, Rhoades HM, Cherek DR. Impulsivity and history of drug dependence. Drug Alcohol Depend. 1998; 50 :137–145. [ PubMed ] [ Google Scholar ]
• Alonso G, Szafarczyk A, Balmefrezol M, Assenmacher I. Immunocytochemical evidence for stimulatory control by the ventral noradrenergic bundle of parvocellular neurons of the paraventricular nucleus secreting corticotropin-releasing hormone and vasopressin in rats. Brain Res. 1986; 397 :297–307. [ PubMed ] [ Google Scholar ]
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4. American Psychiatric Press; Washington. DC: 1994. [ Google Scholar ]
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4. American Psychiatric Press; Washington, DC: 2000. text revision. [ Google Scholar ]
• Aston-Jones G, Delfs JM, Druhan J, Zhu Y. The bed nucleus of the stria terminalis: a target site for noradrenergic actions in opiate withdrawal. In: McGinty JF, editor. Advancing from the ventral striatum to the extended amygdala: implications for neuropsychiatry and drug abuse (series title: Annals of the New York Academy of Sciences. Vol. 877. New York Academy of Sciences; New York: 1999. pp. 486–498. [ PubMed ] [ Google Scholar ]
• Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT. CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat. Psychopharmacology. 1991; 103 :227–232. [ PubMed ] [ Google Scholar ]
• Becker HC, Lopez MF. Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice. Alcohol: Clin Exp Res. 2004; 28 :1829–1838. [ PubMed ] [ Google Scholar ]
• Besson JM. The neurobiology of pain. Lancet. 1999; 353 :1610–1615. [ PubMed ] [ Google Scholar ]
• Blackburn-Munro G, Jensen BS. The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain. Eur J Pharmacol. 2003; 460 :109–116. [ PubMed ] [ Google Scholar ]
• Breese GR, Overstreet DH, Knapp DJ, Navarro M. Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior; inhibition by CRF 1 - and benzodiazepine-receptor antagonists and a 5-HT 1a -receptor agonist. Neuropsychopharmacology. 2005; 30 :1662–1669. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Brown SA, Schuckit MA. Changes in depression among abstinent alcoholics. J Stud Alcohol. 1988; 49 :412–417. [ PubMed ] [ Google Scholar ]
• Brown G, Jackson A, Stephens DN. Effects of repeated withdrawal from chronic ethanol on oral self-administration of ethanol on a progressive ratio schedule. Behav Pharmacol. 1998; 9 :149–161. [ PubMed ] [ Google Scholar ]
• Chance WT, Sheriff S, Peng F, Balasubramaniam A. Antagonism of NPY-induced feeding by pretreatment with cyclic AMP response element binding protein antisense oligonucleotide. Neuropeptides. 2000; 34 :167–172. [ PubMed ] [ Google Scholar ]
• Chu K, Koob GF, Cole M, Zorrilla EP, Roberts AJ. Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF 1 receptor antagonist antalarmin and by CRF 1 , receptor knockout. Pharmacol Biochem Behav. 2007; 86 :813–821. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• de Timary P, Luts A, Hers D, Luminel O. Absolute and relative stability of alexithymia in alcoholic inpatients undergoing alcohol withdrawal: relationship to depression and anxiety. Psychiatry Res. 2008; 157 :105–113. [ PubMed ] [ Google Scholar ]
• Delfs JM, Zhu Y, Druhan JP, Aston-Jones G. Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature. 2000; 403 :430–434. [ PubMed ] [ Google Scholar ]
• Devaud LL, Fritschy JM, Sieghart W, Morrow AL. Bidirectional alterations of GABA A receptor subunit pepetide levels in rat cortex during chronic ethanol consumption and withdrawal. J Neurochem. 1997; 69 :126–130. [ PubMed ] [ Google Scholar ]
• Di Ciano P, Coury A, Depoortere RY, Egilmez Y, Lane JD, Emmett-Oglesby MW, Lepiane FG, Phillips AG, Blaha CD. Comparison of changes in extracellular dopamine concentrations in the nucleus accumbens during intravenous self-administration of cocaine or d-amphetamine. Behav Pharmacol. 1995; 6 :311–322. [ PubMed ] [ Google Scholar ]
• Doyon WM, York JL, Diaz LM, Samson HH, Czachowski CL, Gonzales RA. Dopamine activity in the nucleus accumbens during consummatory phases of oral ethanol self-administration. Alcohol: Clin Exp Res. 2003; 27 :1573–1582. [ PubMed ] [ Google Scholar ]
• Driessen M, Meier S, Hill A, Wetterling T, Langs W, Junghanns K. The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders. Alcohol Alcoholism. 2001; 36 :249–255. [ PubMed ] [ Google Scholar ]
• Epping-Jordan MP, Watkins SS, Koob GF, Markou A. Dramatic decreases in brain reward function during nicotine withdrawal. Nature. 1998; 393 :76–79. [ PubMed ] [ Google Scholar ]
• Fidler TL, Clews TW, Cunningham CL. Reestablishing an intragastric ethanol self-infusion model in rats. Alcohol: Clin Exp Res. 2006; 30 :414–428. [ PubMed ] [ Google Scholar ]
• Fillmore MT, Rush CR. Impaired inhibitory control of behavior in chronic cocaine users. Drug Alcohol Depend. 2002; 66 :265–273. [ PubMed ] [ Google Scholar ]
• Finn DA, Snelling C, Fretwell AM, Tanchuck MA, Underwood L, Cole M, Crabbe JC, Roberts AJ. Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12–41) Alcohol: Clin Exp Res. 2007; 31 :939–949. [ PubMed ] [ Google Scholar ]
• Funk CK, O’Dell LE, Crawford EF, Koob GF. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci. 2006; 26 :11324–11332. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Funk CK, Zorrilla EP, Lee M-J, Rice KC, Koob GF. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol Psychiatry. 2007; 61 :78–86. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Gardner EL, Vorel SR. Cannabinoid transmission and reward-related events. Neurobiol Dis. 1998; 5 :502–533. [ PubMed ] [ Google Scholar ]
• Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, McKinzie D, Morin M, Ciccocioppo R, Heilig M. 3-(4-Chloro-2-morpholin-4-ylthiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine: a novel brain penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. J Neurosci. 2007; 27 :2718–2726. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• George O, Koob GF. Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neurosci Biobehav Rev. 2010 (in press) [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Gilpin NW, Misra K, Koob GF. Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced increases in alcohol drinking. Pharmacol Biochem Behav. 2008; 90 :475–480. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Gilpin NW, Smith AD, Cole M, Weiss F, Koob GF, Richardson HN. Operant behavior and alcohol levels in blood and brain of alcohol-dependent rats. Alcohol: Clin Exp Res. 2009; 33 :2113–2123. [erratum: 34: 382] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002; 159 :1642–1652. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Goodwin DW. Alcoholism: the facts. Oxford University Press; New York: 1981. [ Google Scholar ]
• Green L, Fristoe N, Myerson J. Temporal discounting and preference reversals in choice between delayed outcomes. Psychon Bull Rev. 1994; 1 :383–389. [ PubMed ] [ Google Scholar ]
• Hebb DO. Textbook of psychology. 3. W.B. Saunders; Philadelphia: 1972. [ Google Scholar ]
• Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 2007; 30 :399–406. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Heimer L, Alheid G. Piecing together the puzzle of basal forebrain anatomy. In: Napier TC, Kalivas PW, Hanin I, editors. The basal forebrain: Anatomy to function (series title: advances in experimental medicine and biology) Vol. 295. Plenum Press; New York: 1991. pp. 1–42. [ PubMed ] [ Google Scholar ]
• Heinz A, Lober S, Georgi A, Wrase J, Hermann D, Rey ER, Wellek S, Mann K. Reward craving and withdrawal relief craving: assessment of different motivational pathways to alcohol intake. Alcohol Alcoholism. 2003; 38 :35–39. [ PubMed ] [ Google Scholar ]
• Hemby SE, Martin TJ, Co C, Dworkin SI, Smith JE. The effects of intravenous heroin administration on extracellular nucleus accumbens dopamine concentrations as determined by in vivo microdialysis. J Pharmacol Exp Ther. 1995; 273 :591–598. [ PubMed ] [ Google Scholar ]
• Hernandez G, Hamdani S, Rajabi H, Conover K, Stewart J, Arvanitogiannis A, Shizgal P. Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences. Behav Neurosci. 2006; 120 :888–904. [ PubMed ] [ Google Scholar ]
• Holter SM, Henniger MS, Lipkowski AW, Spanagel R. Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats. Psychopharmacology. 2000; 153 :93–102. [ PubMed ] [ Google Scholar ]
• Ji D, Gilpin NW, Richardson HN, Rivier CL, Koob GF. Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats. Behav Pharmacol. 2008; 19 :1–12. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997; 4 :231–244. [ PubMed ] [ Google Scholar ]
• Khantzian EJ. Understanding addictive vulnerability: an evolving psychodynamic perspective. Neuro-Psychoanalysis. 2003; 5 :5–7. [ Google Scholar ]
• Knapp C. Drinking: a love story. Dial Press; New York: 1996. [ Google Scholar ]
• Knapp DJ, Overstreet DH, Moy SS, Breese GR. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats. Alcohol. 2004; 32 :101–111. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Knapp DJ, Overstreet DH, Breese GR. Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/ γ -aminobutyric acid ligands. Alcohol: Clin Exp Res. 2005; 29 :553–563. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Knapp DJ, Overstreet DH, Breese GR. Baclofen blocks expression and sensitization of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal. Alcohol: Clin Exp Res. 2007; 31 :582–595. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Kohut H. The analysis of the self (series title: the psychoanalytic study of the child) Vol. 4. International Universities Press; New York: 1971. [ Google Scholar ]
• Koob GF. Drugs of abuse: anatomy, pharmacology, and function of reward pathways. Trends Pharmacol Sci. 1992; 13 :177–184. [ PubMed ] [ Google Scholar ]
• Koob GF. Corticotropin-releasing factor, norepinephrine and stress. Biol Psychiatry. 1999; 46 :1167–1180. [ PubMed ] [ Google Scholar ]
• Koob GF. Alcoholism: allostasis and beyond. Alcohol: Clin Exp Res. 2003; 27 :232–243. [ PubMed ] [ Google Scholar ]
• Koob GF. Allostatic view of motivation: implications for psychopathology. In: Bevins RA, Bardo MT, editors. Motivational factors in the etiology of drug abuse (series title: nebraska symposium on motivation) Vol. 50. University of Nebraska Press; Lincoln NE: 2004. pp. 1–18. [ PubMed ] [ Google Scholar ]
• Koob GF. A role for brain stress systems in addiction. Neuron. 2008a; 59 :11–34. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Koob GF. Neurobiology of addiction. In: Galanter M, Kleber HD, editors. Textbook of substance abuse treatment. 4. American Psychiatric Publishing; Washington DC: 2008b. pp. 3–16. [ Google Scholar ]
• Koob GF, Ahmed SH, Boutrel B, Chen SA, Kenny PJ, Markou A, O’Dell LE, Parsons LH, Sanna PP. Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev. 1994; 27 :739–749. [ PubMed ] [ Google Scholar ]
• Koob GF, Bloom FE. Cellular and molecular mechanisms of drug dependence. Science. 1988; 242 :715–723. [ PubMed ] [ Google Scholar ]
• Koob GF, Everitt BJ, Robbins TW. Reward, motivation, and addiction. In: Squire LG, Berg D, Bloom FE, Du Lac S, Ghosh A, Spitzer N, editors. Fundamental Neuroscience. 3. Academic Press; Amsterdam: 2008. pp. 987–1016. [ Google Scholar ]
• Koob GF, Kreek MJ. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry. 2007; 164 :1149–1159. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997; 278 :52–58. [ PubMed ] [ Google Scholar ]
• Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001; 24 :97–129. [ PubMed ] [ Google Scholar ]
• Koob GF, Le Moal M. Plasticity of reward neurocircuitry and the “dark side” of drug addiction. Nature Neurosci. 2005; 8 :1442–1444. [ PubMed ] [ Google Scholar ]
• Koob GF, Le Moal M. Neurobiology of addiction. Academic Press; London: 2006. [ Google Scholar ]
• Koob GF, Le Moal M. Addiction and the brain antireward system. Annu Rev Psychol. 2008; 59 :29–53. [ PubMed ] [ Google Scholar ]
• Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacol Rev. 2010; 35 :217–238. [erratum:35:1051] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Koob GF, Winger GD, Meyerhoff JL, Annau Z. Effects of D-amphetamine on concurrent self-stimulation of forebrain and brain stem loci. Brain Res. 1977; 137 :109–126. [ PubMed ] [ Google Scholar ]
• Koob GF, Lloyd GK, Mason BJ. Development of pharmacotherapies for drug addiction: a Rosetta stone approach. Nature Rev Drug Discov. 2009; 8 :500–515. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Kornelsky C, Esposito RU. Euphorigenic drugs: effects on the reward pathways of the brain. Fed Proc. 1979; 38 :2473–7476. [ PubMed ] [ Google Scholar ]
• Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C. The dysphoric component of stress is encoded by activation of the dynorphin κ -opioid system. J Neurosci. 2008; 28 :407–414. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Le Doux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000; 23 :155–184. [ PubMed ] [ Google Scholar ]
• Logan GD, Schachar RJ, Tannock R. Impulsivity and inhibitory control. Psychol Sci. 1997; 8 :60–64. [ Google Scholar ]
• Lopez MF, Becker HC. Effect of pattern and number of chronic ethanol exposures on subsequent voluntary ethanol intake in C57BL/6J mice. Psychopharmacology. 2005; 181 :688–696. [ PubMed ] [ Google Scholar ]
• Majchrowicz E. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia. 1975; 43 :245–254. [ PubMed ] [ Google Scholar ]
• Markou A, Koob GF. Post-cocaine anhedonia: an animal model of cocaine withdrawal. Neuropsychopharmacology. 1991; 4 :17–26. [ PubMed ] [ Google Scholar ]
• Martin-Solch C, Magyar S, Kunig G, Missimer J, Schultz W, Leenders KL. Changes in brain activation associated with reward processing in smokers and nonsmokers: a positron emission tomography study. Exp Brain Res. 2001; 139 :278–286. [ PubMed ] [ Google Scholar ]
• McBride WJ, Li TK. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol. 1998; 12 :339–369. [ PubMed ] [ Google Scholar ]
• McEwen BS. Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacology. 2000; 22 :108–124. [ PubMed ] [ Google Scholar ]
• Melis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int Rev Neurobiol. 2005; 63 :101–154. [ PubMed ] [ Google Scholar ]
• Merlo-Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F. Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci. 1995; 15 :5439–5447. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Mhatre MC, Pena G, Sieghart W, Ticku MK. Antibodies specific for GABAA receptor alpha subunits reveal that chronic alcohol treatment down-regulates α -subunit expression in rat brain regions. J Neurochem. 1993; 61 :1620–1625. [ PubMed ] [ Google Scholar ]
• Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC. Psychiatric aspects of impulsivity. Am J Psychiatry. 2001; 158 :1783–1793. [ PubMed ] [ Google Scholar ]
• Morzorati SL, Ramchandani VA, Flury L, Li TK, O’Connor S. Self-reported subjective perception of intoxication reflects family history of alcoholism when breath alcohol levels are constant. Alcohol: Clin Exp Res. 2002; 26 :1299–1306. [ PubMed ] [ Google Scholar ]
• Moy SS, Knapp DJ, Criswell HE, Breese GR. Flumazenil blockade of anxiety following ethanol withdrawal in rats. Psychopharmacology. 1997; 131 :354–360. [ PubMed ] [ Google Scholar ]
• Mucha RF, Herz A. Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology. 1985; 86 :274–280. [ PubMed ] [ Google Scholar ]
• Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nature Rev Neurosci. 2001; 2 :119–128. [ PubMed ] [ Google Scholar ]
• Nestler EJ. Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci. 2004; 25 :210–218. [ PubMed ] [ Google Scholar ]
• Nestler EJ. Is there a common molecular pathway for addiction? Nature Neurosci. 2005; 8 :1445–1449. [ PubMed ] [ Google Scholar ]
• Neugebauer V, Li W, Bird GC, Han JS. The amygdala and persistent pain. Neuroscientist. 2004; 10 :221–234. [ PubMed ] [ Google Scholar ]
• O’Dell LE, Roberts AJ, Smith RT, Koob GF. Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure. Alcohol: Clin Exp Res. 2004; 28 :1676–1682. [ PubMed ] [ Google Scholar ]
• Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol. 1954; 47 :419–427. [ PubMed ] [ Google Scholar ]
• Olive MF, Koenig HN, Nannini MA, Hodge CW. Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake. Pharmacol Biochem Behav. 2002; 72 :213–220. [ PubMed ] [ Google Scholar ]
• Overstreet DH, Knapp DJ, Breese GR. Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF 1 , receptors. Pharmacol Biochem Behav. 2004; 77 :405–413. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Overstreet DH, Knapp DJ, Breese GR. Pharmacological modulation of repeated ethanol withdrawal-induced anxiety-like behavior differs in alcohol-preferring P and Sprague-Dawley rats. Pharmacol Biochem Behav. 2005; 81 :122–130. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Pandey SC. The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction. Pharmacol Ther. 2004; 104 :47–58. [ PubMed ] [ Google Scholar ]
• Paterson NE, Myers C, Markou A. Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats. Psychopharmacology. 2000; 152 :440–446. [ PubMed ] [ Google Scholar ]
• Pfeiffer A, Brantl V, Herz A, Emrich HM. Psychotomimesis mediated by κ opiate receptors. Science. 1986; 233 :774–776. [ PubMed ] [ Google Scholar ]
• Piazza PV, Le Moal M. The role of stress in drug self-administration. Trends Pharmacol Sci. 1998; 19 :67–74. [ PubMed ] [ Google Scholar ]
• Potokar J, Coupland N, Glue P, Groves S, Malizia A, Bailey J, Wilson S, Nutt D. Flumazenil in alcohol withdrawal: a double-blind placebo-controlled study. Alcohol Alcoholism. 1997; 32 :605–611. [ PubMed ] [ Google Scholar ]
• Rachlin H, Green L. Commitment, choice and self-control. J Exp Anal Behav. 1972; 17 :15–22. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M. A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry. 2010 (in press) [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Rasmussen DD, Boldt BM, Bryant CA, Mitton DR, Larsen SA, Wilkinson CW. Chronic daily ethanol and withdrawal: 1. Long-term changes in the hypothalamo-pituitary-adrenal axis. Alcohol: Clin Exp Res. 2000; 24 :1836–1849. [ PubMed ] [ Google Scholar ]
• Rassnick S, Heinrichs SC, Britton KT, Koob GF. Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res. 1993; 605 :25–32. [ PubMed ] [ Google Scholar ]
• Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC. Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav. 2005; 84 :53–63. [ PubMed ] [ Google Scholar ]
• Richardson HN, Zhao Y, Fekete EM, Funk CK, Wirsching P, Janda KD, Zorrilla EP, Koob GF. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF 1 ) antagonist. Pharmacol Biochem Behav. 2008; 88 :497–510. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Rimondini R, Arlinde C, Sommer W, Heilig M. Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J. 2002; 16 :27–35. [ PubMed ] [ Google Scholar ]
• Rivier C, Bruhn T, Vale W. Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF) J Pharmacol Exp Ther. 1984; 229 :127–131. [ PubMed ] [ Google Scholar ]
• Roberto M, Cruz MT, Gilpin NW, Sabino V, Schweitzer P, Bajo M, Cottone P, Madamba SG, Stouffer DG, Zorrilla EP, Koob GF, Siggins GR, Parsons LH. Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol Psychiatry. 2010; 67 :831–839. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Roberts AJ, Cole M, Koob GF. Intra-amygdala muscimol decreases operant ethanol self-administration in dependent rats. Alcohol: Clin Exp Res. 1996; 20 :1289–1298. [ PubMed ] [ Google Scholar ]
• Roberts AJ, Heyser CJ, Koob GF. Operant self-administration of sweetened versus unsweetened ethanol: effects on blood alcohol levels. Alcohol: Clin Exp Res. 1999; 23 :1151–1157. [ PubMed ] [ Google Scholar ]
• Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Excessive ethanol drinking following a history of dependence: animal model of allostasis. Neuropsychopharmacology. 2000; 22 :581–594. [ PubMed ] [ Google Scholar ]
• Romach MK, Sellers EM. Management of the alcohol withdrawal syndrome. Annu Rev Med. 1991; 42 :323–340. [ PubMed ] [ Google Scholar ]
• Rossetti ZL, Hmaidan Y, Gessa GL. Marked inhibition of mesolimbic dopamine release: a common feature of ethanol, morphine, cocaine and amphetamine abstinence in rats. Eur J Pharmacol. 1992; 221 :227–234. [ PubMed ] [ Google Scholar ]
• Rossetti ZL, Isola D, De Vry J, Fadda F. Effects of nimodipine on extracellular dopamine levels in the rat nucleus accumbens in ethanol withdrawal. Neuropharmacology. 1999; 38 :1361–1369. [ PubMed ] [ Google Scholar ]
• Russell MAH. What is dependence? In: Edwards G, editor. Drugs and drug dependence. Lexington Books; Lexington MA: 1976. pp. 182–187. [ Google Scholar ]
• Samson HH. Initiation of ethanol-maintained behavior: a comparison of animal models and their implication to human drinking. In: Thompson T, Dews PB, Barrett JE, editors. Neurobehavioral Pharmacology (series title: Advances in Behavioral Pharmacology) Vol. 6. Lawrence Erlbaum; Hillsdale, NJ: 1987. pp. 221–248. [ Google Scholar ]
• Sapru MK, Diamond I, Gordon AS. Adenosine receptors mediate cellular adaptation to ethanol in NG108–15 cells. J Pharmacol Exp Ther. 1994; 271 :542–548. [ PubMed ] [ Google Scholar ]
• Schulteis G, Liu J. Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats. Alcohol. 2006; 39 :21–28. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Schulteis G, Markou A, Gold LH, Stinus L, Koob GF. Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. J Pharmacol Exp Ther. 1994; 271 :1391–1398. [ PubMed ] [ Google Scholar ]
• Schulteis G, Markou A, Cole M, Koob G. Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA. 1995; 92 :5880–5884. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Schulteis G, Hyytia P, Heinrichs SC, Koob GF. Effects of chronic ethanol exposure on oral self-administration of ethanol or saccharin by Wistar rats. Alcohol: Clin Exp Res. 1996; 20 :164–171. [ PubMed ] [ Google Scholar ]
• Shurnan J, Koob GF, Gutstein H. Hyperalgesia in pain treatment: an allostatic perspective. Pain Med 2010 [ Google Scholar ]
• Sifneos PE. The prevalence of ‘alexithymic’ characteristics in psychosomatic patients. Psychother Psychosom. 1973; 22 :255–262. [ PubMed ] [ Google Scholar ]
• Solomon RL, Corbit JD. An opponent-process theory of motivation: I. Temporal dynamics of affect. Psychol Rev. 1974; 81 :119–145. [ PubMed ] [ Google Scholar ]
• Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, Heilig MA. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhrl expression following a history of dependence. Biol Psychiatry. 2008; 63 :139–145. [ PubMed ] [ Google Scholar ]
• Song ZH, Takemori AE. Stimulation by corticotropin-releasing factor of the release of immunoreactive dynorphin A from mouse spinal cords in vitro. Eur J Pharmacol. 1992; 222 :27–32. [ PubMed ] [ Google Scholar ]
• Sterling P, Eyer J. Allostasis: a new paradigm to explain arousal pathology. In: Fisher S, Reason J, editors. Handbook of life stress. Cognition and health. Wiley; Chichester: 1988. pp. 629–649. [ Google Scholar ]
• Taylor GJ, Bagby RM. An overview of the alexithymia construct. In: Bar-On R, Parker JDA, editors. The handbook of emotional intelligence: theory, development, assessment, and application at home, school, and in the workplace. Jossey-Bass; San Francisco: 2000. pp. 40–67. [ Google Scholar ]
• Thorsell A, Slawecki CJ, Ehlers CL. Effects of neuropeptide Y and corticotropin-releasing factor on ethanol intake in Wistar rats: interaction with chronic ethanol exposure. Behav Brain Res. 2005a; 161 :133–140. [ PubMed ] [ Google Scholar ]
• Thorsell A, Slawecki CJ, Ehlers CL. Effects of neuropeptide Y on appetitive and consummatory behaviors associated with alcohol drinking in wistar rats with a history of ethanol exposure. Alcohol: Clin Exp Res. 2005b; 29 :584–590. [ PubMed ] [ Google Scholar ]
• Thorsell A, Rapunte-Canonigo V, O’Dell L, Chen SA, King A, Lekic D, Koob GF, Sanna PP. Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats. Brain. 2007; 130 :1330–1337. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Trzaskowska E, Kostowski W. Further studies on the role of noradrenergic mechanisms in ethanol withdrawal syndrome in rats. Pol J Pharmacol. 1983; 35 :351–358. [ PubMed ] [ Google Scholar ]
• Valdez CR, Zorrilla EP, Roberts AJ, Koob GF. Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence. Alcohol. 2003; 29 :55–60. [ PubMed ] [ Google Scholar ]
• Valdez GR, Sabino V, Koob GF. Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation. Alcohol: Clin Exp Res. 2002; 26 :1494–1501. [ PubMed ] [ Google Scholar ]
• Valdez GR, Platt DM, Rowlett JK, Rüedi-Bettschen D, Spealman RD. κ Agonist-induced reinstatement of cocaine seeking in squirrel monkeys: a role for opioid and stress-related mechanisms. J Pharmacol Exp Ther. 2007; 323 :525–533. [ PubMed ] [ Google Scholar ]
• Valentino RJ, Page ME, Curtis AL. Activation of noradrenergic locus coeruleus neurons by hemodynamic stress is due to local release of corticotropin-releasing factor. Brain Res. 1991; 555 :25–34. [ PubMed ] [ Google Scholar ]
• Valentino RJ, Foote SL, Page ME. The locus coeruleus as a site for integrating corticotropin-releasing factor and noradrenergic mediation of stress responses. In: Tache Y, Rivier C, editors. Corticotropin-releasing factor and cytokines: role in the stress response (series title: Annals of the New York Academy of Sciences. Vol. 697. New York Academy of Sciences; New York: 1993. pp. 173–188. [ PubMed ] [ Google Scholar ]
• Van Bockstaele EJ, Colago EE, Valentino RJ. Amygdaloid corticotropin-releasing factor targets locus coeruleus dendrites: substrate for the co-ordination of emotional and cognitive limbs of the stress response. J Neuroendocrinol. 1998; 10 :743–757. [ PubMed ] [ Google Scholar ]
• Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex. 2000; 10 :318–325. [ PubMed ] [ Google Scholar ]
• Volkow ND, Fowler JS, Wang GJ. Role of dopamine in drug reinforcement and addiction in humans: results from imaging studies. Behav Pharmacol. 2002; 13 :355–366. [ PubMed ] [ Google Scholar ]
• Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Jayne M, Ma Y, Pradhan K, Wong C. Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci. 2007; 27 :12700–12706. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Walker BM, Koob GF. Pharmacological evidence for a motivational role of κ -Opioid systems in ethanol dependence. Neuropsychopharmacology. 2008; 33 :643–652. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Walker BM, Rasmussen DD, Raskind MA, Koob GF. α 1 -Noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol. 2008; 42 :91–97. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Wee S, Koob GF. The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology. 2010; 210 :121–135. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Weiss F, Hurd YL, Ungerstedt U, Markou A, Plotsky PM, Koob GF. Neurochemical correlates of cocaine and ethanol self-administration. In: Kalivas PW, Samson HH, editors. The neurobiology of drug and alcohol addiction (series title: Annals of the New York Academy of Sciences) Vol. 654. New York Academy of Sciences; New York: 1992a. pp. 220–241. [ PubMed ] [ Google Scholar ]
• Weiss F, Markou A, Lorang MT, Koob GF. Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res. 1992b; 593 :314–318. [ PubMed ] [ Google Scholar ]
• Weiss F, Parsons LH, Schulteis G, Hyytia P, Lorang MT, Bloom FE, Koob GF. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996; 16 :3474–3485. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Wikler A. A psychodynamic study of a patient during experimental self-regulated re-addiction to morphine. Psychiatric Q. 1952; 26 :270–293. [ PubMed ] [ Google Scholar ]
• Wolffgramm J, Heyne A. From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat. Behav Brain Res. 1995; 70 :77–94. [ PubMed ] [ Google Scholar ]
• Zald DH, Kim SW. The orbitofrontal cortex. In: Salloway SP, Malloy PF, Duffy JD, editors. The frontal lobes and neuropsychiatric illness. American Psychiatric Press; Washington. DC: 2001. pp. 33–70. [ Google Scholar ]
• Zorrilla EP, Valdez GR, Weiss F. Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats. Psychopharmacology. 2001; 158 :374–381. [ PubMed ] [ Google Scholar ]

Purdue Online Writing Lab Purdue OWL® College of Liberal Arts

Developing Strong Thesis Statements

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These OWL resources will help you develop and refine the arguments in your writing.

The thesis statement or main claim must be debatable

An argumentative or persuasive piece of writing must begin with a debatable thesis or claim. In other words, the thesis must be something that people could reasonably have differing opinions on. If your thesis is something that is generally agreed upon or accepted as fact then there is no reason to try to persuade people.

Example of a non-debatable thesis statement:

This thesis statement is not debatable. First, the word pollution implies that something is bad or negative in some way. Furthermore, all studies agree that pollution is a problem; they simply disagree on the impact it will have or the scope of the problem. No one could reasonably argue that pollution is unambiguously good.

Example of a debatable thesis statement:

This is an example of a debatable thesis because reasonable people could disagree with it. Some people might think that this is how we should spend the nation's money. Others might feel that we should be spending more money on education. Still others could argue that corporations, not the government, should be paying to limit pollution.

Another example of a debatable thesis statement:

In this example there is also room for disagreement between rational individuals. Some citizens might think focusing on recycling programs rather than private automobiles is the most effective strategy.

The thesis needs to be narrow

Although the scope of your paper might seem overwhelming at the start, generally the narrower the thesis the more effective your argument will be. Your thesis or claim must be supported by evidence. The broader your claim is, the more evidence you will need to convince readers that your position is right.

Example of a thesis that is too broad:

There are several reasons this statement is too broad to argue. First, what is included in the category "drugs"? Is the author talking about illegal drug use, recreational drug use (which might include alcohol and cigarettes), or all uses of medication in general? Second, in what ways are drugs detrimental? Is drug use causing deaths (and is the author equating deaths from overdoses and deaths from drug related violence)? Is drug use changing the moral climate or causing the economy to decline? Finally, what does the author mean by "society"? Is the author referring only to America or to the global population? Does the author make any distinction between the effects on children and adults? There are just too many questions that the claim leaves open. The author could not cover all of the topics listed above, yet the generality of the claim leaves all of these possibilities open to debate.

Example of a narrow or focused thesis:

In this example the topic of drugs has been narrowed down to illegal drugs and the detriment has been narrowed down to gang violence. This is a much more manageable topic.

We could narrow each debatable thesis from the previous examples in the following way:

Narrowed debatable thesis 1:

This thesis narrows the scope of the argument by specifying not just the amount of money used but also how the money could actually help to control pollution.

Narrowed debatable thesis 2:

This thesis narrows the scope of the argument by specifying not just what the focus of a national anti-pollution campaign should be but also why this is the appropriate focus.

Qualifiers such as " typically ," " generally ," " usually ," or " on average " also help to limit the scope of your claim by allowing for the almost inevitable exception to the rule.

Types of claims

Claims typically fall into one of four categories. Thinking about how you want to approach your topic, or, in other words, what type of claim you want to make, is one way to focus your thesis on one particular aspect of your broader topic.

Claims of fact or definition: These claims argue about what the definition of something is or whether something is a settled fact. Example:

Claims of cause and effect: These claims argue that one person, thing, or event caused another thing or event to occur. Example:

Claims about value: These are claims made of what something is worth, whether we value it or not, how we would rate or categorize something. Example:

Claims about solutions or policies: These are claims that argue for or against a certain solution or policy approach to a problem. Example:

Which type of claim is right for your argument? Which type of thesis or claim you use for your argument will depend on your position and knowledge of the topic, your audience, and the context of your paper. You might want to think about where you imagine your audience to be on this topic and pinpoint where you think the biggest difference in viewpoints might be. Even if you start with one type of claim you probably will be using several within the paper. Regardless of the type of claim you choose to utilize it is key to identify the controversy or debate you are addressing and to define your position early on in the paper.

The Thesis Statement in a Persuasive Text

Alys Avalos-Rivera

In another chapter, we discussed the features of an informational essay. In this chapter, we will guide you to understand the essential elements of a similar type of academic text: the persuasive essay. Although informational and persuasive writing follow similar principles such as an orderly presentation of ideas that should be supported with evidence (e.g. facts, arguments, or examples), their purposes differ. The objective is written to take a stance (specific point of view) with respect to a controversial topic and persuade the audience to adopt the writer’s position. Because of this difference, the thesis statement of the persuasive essay needs to introduce the writer’s position in the controversy featured in the essay. Also, the preview of the essay’s structure should outline the arguments that the author will use to support his/her stance.

Should the US drinking age be lowered?

In the US, drinking alcoholic beverages is illegal for people under 21 years of age (minimum legal drinking age or MLDA). This law has long caused a great deal of disagreement and debates. While some people think it is paradoxical that young people of 18 cannot enter a bar but still go to war, others believe that the law is the best way to keep youth away from irresponsible and heavy drinking episodes (also called binge drinking). The following texts were written by readers of the New York Times” Room for Debate page to express their opinions about the subject. [1]

• Read the comments and underline the readers’ main arguments (reasons to support one position or the other).
• Identify which readers are against lowering the minimum drinking age (CON) and which are in favor (PRO)?
• Which arguments seem the least convincing? Which are the most persuasive? Why?

Content focus: Rating thesis statements

Considering these features, in the following task you will analyze how six college students drafted their thesis statements for a persuasive essay on the MLDA controversy. In the prompt used by the instructor for this assignment, students were required to address the following purposes:

• Present the PROs and CONs of the MLDA to a group of college students’ parents.
• Persuade the parents to vote in favor of lowering the MLDA to 18 years of age.

In other words, the writers need to take a stance on the issue. Read the Thesis Statement and assess how well each one fulfills the purposes given above and to what extent. Rate the Thesis Statement using a scale from 1 to 6, where 6 will stand for the best Thesis Statement and 1 will be given to the poorest. Be prepared to explain the reasons you have to support your rating.

a. The United States has more accidents caused by drivers under the influence of alcohol than other countries where there is no MLDA (        )

b. Young people should be allowed to drink without legal restrictions based on their age, which is ridiculous (        )

c. Parents should teach their children how to drink alcohol in moderation.  (        )

d. Lowering the MLDA will allow parents to introduce their children to alcohol use under the supervision and reduce the rate of accidents caused by drunken drivers (        )

e. A reduction in the MLDA will help neutralize teenagers’ obsession with drinking, allow parents to monitor their children first encounters with alcohol, and reduce the rate of accidents caused by irresponsible drinking.   (        )

f. Having the MLDA fixed at 21 is only increasing young people’s fascination with drinking in unsafe environments and using false IDs.     (        )

Guidelines for a thesis statement

What should be considered when drafting a thesis statement for an essay that aims to persuade the audience to take a stand in a controversial issue? Think of some possible guidelines to write an effective persuasive TS taking into account the following:

• How should you address your audience?
• Where in your text should you introduce your stance?
• What language features (words, phrases) could be useful?
• How can you connect your TS with the main arguments you will use in your essay?

Write your guidelines below and discuss them with your colleagues and your instructor:

In some of the thesis statements listed above, the writers use modal verbs such as will and should . The first one ( will ) is used to predict the results that could be achieved if the authorities follow a specific course of action regarding the MLDA. The second one ( should ) is used to recommend what should be done with respect to the MLDA. These and other modal verbs that express advice, convey an obligation, or predict an outcome are often used to introduce the writer’s stance because they are useful to express the speaker’s desires, or his/her ideas of how the world should be. Other modal verbs that are also used with these purposes are: must, can, could, ought to, and also the semi-modal have to .

When using modal verbs to compose your thesis statement, however, you should be careful to select the one that best represents your purpose. The meaning of your thesis statement can change a great deal if you use one or the other. Read the following examples and explain how the meaning has changed with each modal (in bold):

*Although ought to and must are accepted as standard forms, they are not used in Academic English very often because they imply a strong and categorical position. Scientists usually abstain from categorical statements because these expressions do not convey that the writer remains open to new possibilities. Scientist prefer to maintain a more open attitude in their writing in case new evidence is discovered in the future that can change their points of view about the world.

Although the participants in the Room for Debate’s and Star Wars pages hold different points of view regarding very different topics, they all engaged in their online discussions with a common purpose: persuading their audience of their point of view. They do so in a succinct fashion because their audience does not usually invest much time in reading blog posts that are too long and complex. Therefore, effective blog/forum posters try to be direct and present one single point per post. On the contrary, academic persuasive writing needs to be more detailed and provide the audience with more than just the author’s point of view.

• https://www.nytimes.com/roomfordebate/2015/02/10/you-must-be-21-to-drink ↵

The Thesis Statement in a Persuasive Text Copyright © 2020 by Alys Avalos-Rivera is licensed under a Creative Commons Attribution 4.0 International License , except where otherwise noted.

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Alcoholism Introduction Thesis Statement: Alcoholism can be very...

Alcoholism Introduction Thesis Statement: Alcoholism can be very addictive and affect life in various ways. I. Background: Alcohol is a part of our life and it is our choice to maintain it at a professional level. It has its ups and down in so many different ways that we can't even imagine. II. Effect on marriage A. Fertility issue 1. " Drinking excessively can prevent a woman from getting pregnant, and it damages a man's sperm". B. Fear and anxiety 1. "Excessive worry and fear can lead to the spouse developing anxiety disorders and depression" III. Abuse A. Psychical signs 1. The psychological signs of alcohol abuse emerge when the substance interferes with usual brain functioning. The most common emotional B. Different Signs 1. " Rapidly mood changing, increased irritability, anger and aggression". 2. "Decreased self care, poor hygiene". IV. Trauma A. Gender 1. "Gender is an important factor as well. Women who have PTSD at some point in their lives are 2.5 times more likely to also have alcohol abuse or dependence than women who never have PTSD". 2. "Men are 2.0 times more likely to have alcohol problems if they have PTSD than men who never do not have PTSD". 

i need complete essay on this topic according to the requirements 

Answer & Explanation

The most frequently used addictive substance is alcohol. Adult alcoholism is a common diagnosis, and millions more people engage in harmful habits like binge drinking that may develop into alcohol misuse disorders. Unfortunately, alcohol abuse has detrimental effects on others other than the one who is abusing it. This behavior places a burden on friends, family, and even kids. The concept of alcoholism can be distorted since the mainstream media frequently downplays the seriousness of alcohol misuse and instead promotes it as a socially acceptable behavior. Although there can be a fine line between having a drinking problem and having an alcohol addiction, both are unhealthy behaviors that can lead to problems with family, finances, friends, and other aspects of a person's life in addition to difficulties with work or career. Alcohol is a depressant of the central nervous system. This indicates that the medication slows brain activity. Your mood, conduct, and self-control may change as a result. It may impair one's memory and ability to think coherently. Each of us, specifically in the marriage life, is affected by alcohol in many different ways. Within a family, alcohol abuse and alcohol use disorder, which is the medical term for an alcohol addiction, can cause strife or even lead to the dissolution of the marriage. As a result, those who abuse alcohol run up huge debts, start arguments, neglect their kids, and generally harm the wellbeing of the people they care about. Family members may eventually start to exhibit codependency characteristics, unintentionally maintaining the addiction despite the harm it causes. Additionally, drinking reduces male fertility. Less likely to become pregnant are female partners of males who consume large amounts of alcohol. Alcohol can disrupt hormone levels and the way the testes work, which prevents sperm from growing normally and limits their ability to migrate toward an egg. This occurs because alcohol prevents the liver from adequately metabolizing vitamin A, which is essential for the development of sperm. And whether you're trying for a kid or not, alcohol can have an impact on your sexual life. Excessive drinking can also negatively impact a man's ability to perform in bed, leading to impotence and a loss of sexual drive. Alcohol is pain medication. In the beginning, it may help you feel less inhibited10,11 and slow down activities in your brain and central nervous system. However, these benefits quickly wear off. In fact, drinking alcohol while you're anxious can make matters worse. If you consistently consume large amounts of alcohol, your central nervous system will eventually become accustomed to the depressant effects of the alcohol. As a result, your brain will be harmed if your alcohol intake abruptly reduces. As the alcohol leaves your system, you may immediately enter "fight or flight" mode, which is a response similar to an anxiety illness. 

Alcoholism is a disease that can affect anyone, regardless of age, gender, race, physical appearance, or religious views. Alcoholism can develop suddenly and violently or it can develop slowly over time. There are several treatment alternatives available to help you get your life back on track, regardless of when or how a drinking issue begins. The best chance for long-lasting sobriety is to seek expert assistance. Alcohol consumption and acquisition become a person's top priorities as they develop dependence, with all other responsibilities falling to the wayside. This frequently results in the person becoming more and more dependent on alcohol to provide the desired effects. Additionally, it leads to physical dependence, which results in withdrawal symptoms when someone tries to reduce or stop drinking. The physical signs of alcoholism might differ from person to person, although some affects. Some physical signs are dishevelled appearance, Either gaining or losing weight, Redness in the face, especially the nose and cheeks, Liver problems like cirrhosis. And it is also cause of poor hygiene and less self-care. 

People frequently report using alcohol at some time after a traumatic experience to treat their symptoms of anxiety, irritability, and depression. Alcohol may help with these symptoms because it makes up for endorphin activity that is reduced after a traumatic event. The amount of endorphins in the brain increases minutes after being exposed to a distressing incident. Endorphin levels remain high during the trauma and aid in numbing the mental and physical pain of the trauma. However, endorphin levels steadily decline after the shock is done, which may result in an interval of endorphin withdrawal that can continue for hours or days. Endorphin depletion at this time frame could result in emotional suffering and lead to the development of further PTSD symptoms (PTSD). Drinking after trauma may be utilized to compensate for this endorphin withdrawal and hence prevent the related emotional suffering because alcohol consumption boosts endorphin activity. This paradigm has significant effects on how PTSD and alcoholism are treated. 

One key distinction between having a "drinking problem" and having an alcohol addiction is the capacity to step back and stop. Heavy drinking, binge drinking, underage consumption, and pregnant women are all examples of excessive drinking, according to the National Institute on Alcohol Abuse and Alcoholism (NIH). Men who drink heavily are those who consume more than five drinks in a single sitting and more than 15 drinks per week. Four drinks in one session and more than eight in a week are the norm for women. These people might be categorized as "nearly alcoholics" since they can still step back, evaluate their situation, and make the necessary corrections. Whether you or someone you care about has a drinking problem or an addiction to alcohol, they should seek treatment right away to prevent their habits from getting out of hand. Alcohol-dependent people don't necessarily need to abstain from alcohol, but counseling can often help them figure out why they drink so much. Many people who struggle with alcoholism use alcohol as a bad coping technique or to mask their feelings of anxiety, melancholy, and low self-esteem. Without notice, a drinking issue can swiftly develop into an addiction.

Approach to solving the question: analyzation and summarizing

Detailed explanation: It is all about alcoholism and the effects of it. It is in a essay form because it's on the instruction.

Examples: examples are given above.

Key references: https://www.pinelandsrecovery.com/definition-of-alcoholism/ 

Some explanation are opinion based and based on my thoughts and insights.

I hope it helps and considered ' cause I don't know if I need to complete the given reference or just explain it all in a essay form. So I just explain it in a essay form because it's on the instructions. Thank you and God bless you!

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