Disease theory of alcoholism

Alcohol Dependence
Classification and external resources
Specialty psychiatry
ICD-10 F10.2
ICD-9-CM 303
A 1904 advertisement labeling alcoholism a "disease"

The modern disease theory of alcoholism states that problem drinking is sometimes caused by a disease of the brain, characterized by altered brain structure and function.

The American Medical Association (AMA) had declared that alcoholism was an illness in 1956. In 1991, The AMA further endorsed the dual classification of alcoholism by the International Classification of Diseases under both psychiatric and medical sections.

Theory

Alcoholism is a chronic problem. However, if managed properly, damage to the brain can be stopped and to some extent reversed.[1]  In addition to problem drinking, the disease is characterized by symptoms including an impaired control over alcohol, compulsive thoughts about alcohol, and distorted thinking.[2] Alcoholism can also lead indirectly, through excess consumption, to physical dependence on alcohol, and diseases such as cirrhosis of the liver.

The risk of developing alcoholism depends on many factors, such as environment. Those with a family history of alcoholism are more likely to develop it themselves (Enoch & Goldman, 2001); however, many individuals have developed alcoholism without a family history of the disease. Since the consumption of alcohol is necessary to develop alcoholism, the availability of and attitudes towards alcohol in an individual's environment affect their likelihood of developing the disease. Current evidence indicates that in both men and women, alcoholism is 50–60% genetically determined, leaving 40-50% for environmental influences.[3]

In a review in 2001, McLellan et al. compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. They found that genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders, providing evidence that drug (including alcohol) dependence is a chronic medical illness.[4]

Genetics and environment

According to the theory, genes play a strong role in the development of alcoholism.

Twin studies, adoption studies, and artificial selection studies have shown that a person's genes can predispose them to developing alcoholism. Evidence from twin studies show that concordance rates for alcoholism are higher for monozygotic twins than dizygotic twins—76% for monozygotic twins and 61% for dizygotic twins.[5] However, female twin studies demonstrate that females have much lower concordance rates than males.[5] Reasons for gender differences may be due to environmental factors, such as negative public attitudes towards female drinkers.[6] Twin studies suggest that males are more likely to have a genetic predisposition for alcoholism. However, this does not suggest that a male who does have a genetic predisposition will become an alcoholic. Sometimes the individual may never encounter an environmental trigger that leads to alcoholism.

Adoption studies also suggest a strong genetic tendency towards alcoholism. Studies on children separated from their biological parents demonstrates that sons of alcoholic biological fathers were more likely to become alcoholic, even though they have been separated and raised by non alcoholic parents.[5] Female show similar results, but to a lesser degree.

In artificial selection studies, specific strains of rats were bred to prefer alcohol. These rats preferred drinking alcohol over other liquids, resulting in a tolerance for alcohol and exhibited a physical dependency on alcohol.[5] Rats that were not bred for this preference did not have these traits (Lumeng, Murphy, McBride, & Li, 1995).[5] Upon analyzing the brains of these two strains of rats, it was discovered that there were differences in chemical composition of certain areas of the brain. This study suggests that certain brain mechanisms are more genetically prone to alcoholism.

The convergent evidence from these studies present a strong case for the genetic basis of alcoholism.

History

Historians debate who has primacy in arguing that habitual drinking carried the characteristics of a disease. Some note that Scottish physician Thomas Trotter was the first to characterize excessive drinking as a disease, or medical condition.[7]

Others point to American physician Benjamin Rush (1745–1813), a signatory to the United States Declaration of Independence — who understood drunkenness to be what we would now call a "loss of control" — as possibly the first to use the term "addiction" in this sort of meaning.[8]

My observations authorize me to say, that persons who have been addicted to them, should abstain from them suddenly and entirely. 'Taste not, handle not, touch not' should be inscribed upon every vessel that contains spirits in the house of a man, who wishes to be cured of habits of intemperance.
Levine, H.G., The Discovery of Addiction: Changing Conceptions of Habitual Drunkenness in America [8]

Rush argued that "habitual drunkenness should be regarded not as a bad habit but as a disease", describing it as "a palsy of the will".[9] Rush expounded his views in a book published in 1808.[10] His views are described by Valverde[11] and by Levine:[8]

Swedish physician Magus Huss coined the term "alcoholism" in his book Alcoholismus chronicus.[12] Some argue he was the first to systematically describe the physical characteristics of habitual drinking and claim that it was a disease. However, this came decades after Rush and Trotter wrote their works, and some historians argue that the idea that habitual drinking was a diseased state emerged earlier.[13]

Given this controversy, the best one can say is that the idea that habitual alcohol drinking was a disease had become more acceptable by the middle of the nineteenth century, although many writers still argued it was a vice, a sin, and not the purview of medicine but of religion.[14]

Between 1980 and 1991, medical organizations, including the AMA, worked together to establish policies regarding their positions on the disease theory. These policies were developed in 1987 in part because third-party reimbursement for treatment was difficult or impossible unless alcoholism were categorized as a disease. The policies of the AMA, formed through consensus of the federation of state and specialty medical societies within their House of Delegates, state, in part:

"The AMA endorses the proposition that drug dependencies, including alcoholism, are diseases and that their treatment is a legitimate part of medical practice."

In 1991, the AMA further endorsed the dual classification of alcoholism by the International Classification of Diseases under both psychiatric and medical sections.

Controlled drinking

The disease theory is often interpreted as implying that problem drinkers are incapable of returning to 'normal' problem free drinking, and therefore that treatment should focus on total abstinence. Some critics have used evidence of controlled drinking in formerly dependent drinkers to dispute the disease theory of alcoholism.

The first major empirical challenge to this interpretation of the disease theory followed a 1962 study by Dr. D. L. Davies.[15] Davies' follow-up of 93 problem drinkers found that 7 of them were able to return to "controlled drinking" (less than 7 drinks per day for at least 7 years). Davies concluded that "the accepted view that no alcohol addict can ever again drink normally should be modified, although all patients should be advised to aim at total abstinence"; After the Davies study, several other researchers reported cases of problem drinkers returning to controlled drinking.[16][17][18][19][20][21][22][23]

In 1976, a major study commonly referred to as the RAND report, published evidence of problem drinkers learning to consume alcohol in moderation.[24] The publication of the study renewed controversy over how people suffering a disease which reputedly leads to uncontrollable drinking could manage to drink controllably. Subsequent studies also reported evidence of return to controlled drinking.[25][26][27][28][29] Similarly, according to a 2002 National Institute on Alcohol Abuse and Alcoholism (NIAAA) study, about one of every six (18%) of alcohol dependent adults in the U.S. whose dependence began over one year previously had become "low-risk drinkers" (less than 14 drinks per week and 5 drinks per day for men, or less than 7 per week and 4 per day for women). This modern longitudinal study surveyed more than 43,000 individuals representative of the U.S. adult population, rather than focusing solely on those seeking or receiving treatment for alcohol dependence. "Twenty years after onset of alcohol dependence, about three-fourths of individuals are in full recovery; more than half of those who have fully recovered drink at low-risk levels without symptoms of alcohol dependence." [30]

However, many researchers have debated the results of the smaller studies. A 1994 followup of the original 7 cases studied by Davies suggested that he "had been substantially misled, and the paradox exists that a widely influential paper which did much to stimulate new thinking was based on faulty data."[31] The most recent study, a long-term (60 year) follow-up of two groups of alcoholic men by George Vaillant at Harvard Medical School concluded that "return to controlled drinking rarely persisted for much more than a decade without relapse or evolution into abstinence."[32] Vaillant also noted that "return-to-controlled drinking, as reported in short-term studies, is often a mirage."

The second RAND study, in 1980, found that alcohol dependence represents a factor of central importance in the process of relapse. Among people with low dependence levels at admission, the risk of relapse appears relatively low for those who later drank without problems. But the greater the initial level of dependence, the higher the likelihood of relapse for nonproblem drinkers. (Table 7.8 pg. 152) The second RAND study findings have been strengthened by subsequent research by Dawson et al 2005 which found that severity was associated positively with the likelihood of abstinent recovery and associated negatively with the likelihood of non-abstinent recovery or controlled drinking. Other factors such as a significant period of abstinence or changes in life circumstances were also identified as strong influences for success in a book on Controlled Drinking published in 1981.[33]

Legal considerations

In 1988, the US Supreme Court upheld a regulation whereby the Veterans' Administration was able to avoid paying benefits by presuming that primary alcoholism is always the result of the veteran's "own willful misconduct." The majority opinion written by Justice Byron R. White echoed the District of Columbia Circuit's finding that there exists "a substantial body of medical literature that even contests the proposition that alcoholism is a disease, much less that it is a disease for which the victim bears no responsibility".[34] He also wrote: "Indeed, even among many who consider alcoholism a "disease" to which its victims are genetically predisposed, the consumption of alcohol is not regarded as wholly involuntary." However, the majority opinion stated in conclusion that "this litigation does not require the Court to decide whether alcoholism is a disease whose course its victims cannot control. It is not our role to resolve this medical issue on which the authorities remain sharply divided." The dissenting opinion noted that "despite much comment in the popular press, these cases are not concerned with whether alcoholism, simplistically, is or is not a "disease.""[35]

The American Bar Association "affirms the principle that dependence on alcohol or other drugs is a disease."[36]

Current acceptance

Alcoholism is a disease with a known pathology and an established biomolecular signal transduction pathway[37] which culminates in ΔFosB overexpression within the D1-type medium spiny neurons of the nucleus accumbens;[37][38][39] when this overexpression occurs, ΔFosB induces the addictive state.[37][38][39]

In 2004, the World Health Organisation published a detailed report on alcohol and other psychoactive substances entitled "Neuroscience of psychoactive substance use and dependence".[40] It stated that this was the "first attempt by WHO to provide a comprehensive overview of the biological factors related to substance use and dependence by summarizing the vast amount of knowledge gained in the last 20-30 years. The report highlights the current state of knowledge of the mechanisms of action of different types of psychoactive substances, and explains how the use of these substances can lead to the development of dependence syndrome." The report states that "dependence has not previously been recognized as a disorder of the brain, in the same way that psychiatric and mental illnesses were not previously viewed as being a result of a disorder of the brain. However, with recent advances in neuroscience, it is clear that dependence is as much a disorder of the brain as any other neurological or psychiatric illness."

The American Society of Addiction Medicine and the American Medical Association both maintain extensive policy regarding alcoholism. The American Psychiatric Association recognizes the existence of "alcoholism" as the equivalent of alcohol dependence. The American Hospital Association, the American Public Health Association, the National Association of Social Workers, and the American College of Physicians classify "alcoholism" as a disease.

In the US, the National Institutes of Health has a specific institute, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), concerned with the support and conduct of biomedical and behavioral research on the causes, consequences, treatment, and prevention of alcoholism and alcohol-related problems. It funds approximately 90 percent of all such research in the United States. The official NIAAA position is that "alcoholism is a disease. The craving that an alcoholic feels for alcohol can be as strong as the need for food or water. An alcoholic will continue to drink despite serious family, health, or legal problems. Like many other diseases, alcoholism is chronic, meaning that it lasts a person's lifetime; it usually follows a predictable course; and it has symptoms. The risk for developing alcoholism is influenced both by a person's genes and by his or her lifestyle."[41]

Criticism

Some physicians, scientists and others have rejected the disease theory of alcoholism on logical, empirical and other grounds.[42][43][44][45][46][47] Indeed, some addiction experts such as Stanton Peele are outspoken in their rejection of the disease model, and other prominent alcohol researchers such as Nick Heather have authored books intending to disprove the disease model.[48]

Some critics of the disease model argue alcoholism still involves choice, not total loss of control, and stripping alcohol abusers of their choice, by applying the disease concept, is a threat to the health of the individual; the disease concept gives the substance abuser an excuse. A disease cannot be cured by force of will; therefore, adding the medical label transfers the responsibility from the abuser to caregivers. Inevitably the abusers become unwilling victims, and just as inevitably they take on that role. They argue that the disease theory of alcoholism exists only to benefit the professionals' and governmental agencies responsible for providing recovery services, and the disease model has not offered a solution for those attempting to stop abusive alcohol and drug use.[49]

These critics hold that by removing some of the stigma and personal responsibility the disease concept actually increases alcoholism and drug abuse and thus the need for treatment.[49] This is somewhat supported by a study which found that a greater belief in the disease theory of alcoholism and higher commitment to total abstinence to be factors correlated with increased likelihood that an alcoholic would have a full-blown relapse (substantial continued use) following an initial lapse (single use).[50] However, the authors noted that "the direction of causality cannot be determined from these data. It is possible that belief in alcoholism as a loss-of-control disease predisposes clients to relapse, or that repeated relapses reinforce clients' beliefs in the disease model."

A national study of doctors in the United States reported in The Road to Recovery asked them what proportion of alcoholism is a disease and what proportion is a personal weakness. The average proportion thought to be personal weakness was 31 percent. Significantly, only 12 percent of doctors considered alcoholism to be 100 percent a disease.[51]

Another study found that only 25 percent of physicians believed that alcoholism is a disease. The majority believed alcoholism to be a social or psychological problem instead of a disease.[52]

A survey of physicians at an annual conference of the International Doctors in Alcoholics Anonymous reported that 80 percent believe that alcoholism is merely bad behavior instead of a disease. (Barrier to Treatment. Alcoholmd – Information About Alcohol and Medicine)

Dr. Thomas R. Hobbs says that "Based on my experiences working in the addiction field for the past 10 years, I believe many, if not most, health care professionals still view alcohol addiction as a willpower or conduct problem and are resistant to look at it as a disease." (T.R. Hobbs. Managing Alcoholism as a Disease. Physician's News Digest, 1998.)

Alcoholics-Anonymous says that "Some professionals will tell you that alcoholism is a disease while others contend that it is a choice" and "some doctors will tell you that it is in fact a disease." (Alcoholics-Anonymous. What Is Alcoholism? www.alcoholics-anonymous.com/what-is-alcoholism.htm)[53]

Dr. Lynn Appleton says that "Despite all public pronouncements about alcoholism as a disease, medical practice rejects treating it as such. Not only does alcoholism not follow the model of a 'disease,' it is not amenable to standard medical treatment." She says that "Medical doctors' rejection of the disease theory of alcoholism has a strong basis in the biomedical model underpinning most of their training" and that "medical research on alcoholism does not support the disease model." (Lynn M. Appleton. Rethinking medicalization. Alcoholism and anomalies. Chapter in editor Joel Best's Images of Issues. Typifying Contemporary Social Problems. NY: Aldine De Gruyter, 1995, page 65 and page 69. 2nd edition

"Many doctors have been loath to prescribe drugs to treat alcoholism, sometimes because of the belief that alcoholism is a moral disorder rather than a disease," according to Dr. Bankole Johnson, Chairman of the Department of Psychiatry at the University of Virginia.[54] Dr Johnson's own pioneering work has made important contributions to the understanding of alcoholism as a disease.[55]

Certain medications including opioid antagonists such as naltrexone have been shown to be effective in the treatment of alcoholism, although research has not yet demonstrated long-term efficacy.[56]

Frequency and quantity of alcohol use are not related to the presence of the condition; that is, people can drink a great deal without necessarily being alcoholic, and alcoholics may drink minimally or infrequently.[2][57]

Alcoholism Treatment

The following are suggested courses of action for alcoholics who are ready and willing to treat their addiction through proactive measures:

Intervention:The medical community recommends executing an intervention upon the addicted individual as the first step of the process. An intervention normally consists of family and friends of the addicted individual uniting in a joined effort to encourage the addicted person to seek treatment. In addition to alcoholism an intervention can similarly be used to address other self-destructive addictive behaviors such as drug abuse, gambling, compulsive eating, or self-harm. The medical community recognizes that carefully planned and executed interventions have the highest rate of success in getting addicted individuals to agree to receiving treatment. A licensed interventionist will prep the family, facilitate the intervention, and (many times) assist in transporting the person directly to their respective detox or treatment center.[58]

Medical treatment: Intensive Inpatient treatment for alcoholism is most likely to produce effective change in the alcoholic. Catering to alcoholics through medical treatment in conjunction with the twelve steps dates back to 1948. Coyle Foundation authorized the purchase of the Power family farm in Center City, Minnesota, and in turn sold the property to a charitable hospital corporation in formation, to be called "Hazleden." The original treatment team helped pioneer the integration of the twelve-step program into the treatment community, making it the pillar of their approach in their efforts to helping patients recover. In 2014, Hazelden announced a merger with the Betty Ford Center and became officially known as the Hazelden Betty Ford Foundation. It currently operates under the leadership of CEO Mark Mishek and maintains status as one of the premier drug alcohol abuse treatment centers in North America. Other treatment facilities across the nation offer programs modeled off of those at Hazelden. However, regardless of the approach they take, all treatment centers are alike in the sense that they strive to help patients achieve maintained sobriety.[59]

Length of Treatment: Inpatient treatment facilities that have adapted the twelve-step program range in lengths of stay that vary between 15–90 days of intensive rehabilitation for the addicted person. However, those who experience success in sustained sobriety often maintain meeting attendance for the duration of their life. A.A. supports the idea that no matter how long one has remained abstinent, they will never be cured of this disease. Thus, it is necessary to continually treat it in order to reduce the risk of relapse.

Alcoholics Anonymous: Alcoholics Anonymous is the most popular, widely recognized course of action for those who set out to achieve sobriety. Its focus lies in the twelve-step program that was coined by Bill Wilson in 1935. Membership requirements are simple: have a desire to stop drinking. By engaging in the most important parts of the program (i.e., attending meetings, getting a sponsor, working the twelve steps, and engaging in fellowship with others), many have been successful in maintaining sustained sobriety. A.A. is built upon the idea that by providing support for other struggling alcoholics, the person can enjoy a sense of fulfillment and responsibility in their sobriety. Since many people view addiction as a shameful affliction, its members benefit from having a safe place to talk about issues related to their struggles with alcoholism in a judgment-free environment. In metropolitan cities like Chicago, there are hundreds of AA meetings to choose from all over the city that vary in length and format.[60]

Alternate forms of treatment: For those who have tried and failed using a twelve step program or do not wish to participate in one, several other treatment options exist. Other recovery support groups have formed recently, such as Smart Recovery, SOS, and Moderation Management, each with a more scientific basis of treatment, unlike the spiritual approach of AA. As well, advances in Pharmaceutical medications are offering a solution to some alcoholics in the form of anti-craving medications like Naltrexone, Acamprosate, and Disulfiram. These medications seek to alleviate the effects of alcoholism and reduce the phenomena of craving. In contrast, some people prefer the non-pharmaceutical approach. Meditation, acupuncture, hypnosis, yoga, are just a few alternative therapies that have proved effective in helping alcoholics alleviate stress and divert obsessions to drink. Although Alcoholics Anonymous is the most widely recognized option to seek recovery, its success rates are unclear, and largely debated. Since the program is built on a foundation that advocates for anonymity, records on membership numbers and success rates are not kept. Accordingly, any statistics on success rates derived from or ascribed to A.A. are based on mere estimations.[61]

Beyond treatment: Regardless of what method a person decides to employ to assist in their efforts to get sober, life beyond the initial steps will be difficult. There are many options that increase the success rate of maintained sobriety after leaving treatment. Some of these suggested follow-ups include, but are not limited to: follow-up intensive outpatient program, psychiatric care, and individual talk therapy. Many treatment facilities also refer their clients to recovery homes, so their clients can make a less drastic, safer transition back into everyday life. Sober living homes often maintain strict curfews, administer random drug tests to residents, and employ rules that encourage habits conducive to a sober life. Statistically, people who regularly attend A.A. or non-12 step programs, such as Smart Recovery, and live in sober environments for extended periods of time, have the best chance at success.

See also

References

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  11. Valverde, M., Diseases of the Will: Alcohol and the Dilemmas of Freedom, Cambridge University Press, (Cambridge), 1998.
  12. Hasso Spode has championed the work of C. von Brühl-Cramer on addiction (Trunksucht) from 1819 to be seen as the first consistent "paradigm" of alcohol addiction. See the discussion in the ADHS Forum in the Social History of Alcohol and Drugs: An Interdisciplinary Journal 20 (2005): 105-40 where several addiction historians discuss the changing attitudes of alcohol, tobacco and other drugs and the origins of their ideas
  13. Along with Levine, see Roy Porter ("Drinking Man's Disease: the 'Pre-History' of Alcoholism in Georgian Britain," British Journal of Addiction 80 (1985): 385-96) who places the idea to emerge with Trotter, Jessica Warner ["'Resolved to Drink No More': Addiction as a preindustrial construct" Journal of Studies on Alcohol 55 (1994): 685-91] who uses a narrow reading of 17th century sermons to place it in the 1600s, Peter Ferentzy ["From Sin to Disease: Differences and similarities between past and current conceptions on 'chronic drunkenness'" Contemporary Drug Problems 28 (2001): 362-90] who successfully challenges Warner's argument by showing that the term "disease" was applied to many conditions that had little to do with physical debility, and James Nicholls ["Vinum Britannicum: The 'Drink Question' in Early Modern England" Social History of Alcohol and Drugs: An interdisciplinary Journal 22 (2008): 6-25] who draws it together and argues that the idea emerged at different times in different places.
  14. See, for example, books with such telling titles as John Edwards Todd, Drunkenness, a Vice--not a Disease (1882).
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  38. 1 2 Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am J Drug Alcohol Abuse 40 (6): 428–437. doi:10.3109/00952990.2014.933840. PMID 25083822. Using control drugs implicated in both ΔFosB induction and addiction (ethanol and nicotine), similar ΔFosB expression was apparent when propofol was given ...
    ΔFosB as a therapeutic biomarker
    The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. If ΔFosB detection is indicative of chronic drug exposure (and is at least partly responsible for dependence of the substance), then its monitoring for therapeutic efficacy in interventional studies is a suitable biomarker (Figure 2). Examples of therapeutic avenues are discussed herein. ...

    Conclusions
    ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
  39. 1 2 Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 (4): 431–443. PMC 3898681. PMID 24459410. DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... A large body of literature has demonstrated that such ΔFosB induction in D1-type NAc neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 Many other ΔFosB targets have been shown to mediate the ability of certain drugs of abuse to induce synaptic plasticity in the NAc and associated changes in the dendritic arborization of NAc medium spiny neurons, as will be discussed below.
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