Both animal and human models of alcoholism etiology have focused on biobehavioral response to alcohol as a potential marker of alcoholism risk vulnerability and disease progression. Alcoholism has been conceptualized in neurobiological models as a transition from positive reinforcement (i.e., """"""""drinking to feel good"""""""") to negative reinforcement (i.e., """"""""drinking not to feel bad or to feel normal""""""""), representing a cycl of progressive neurobiological dysregulation. Alcohol administration studies in the human laboratory allow for the translation of preclinical theory to clinical populations through examination of the subjective response to alcohol (comprising stimulation, sedation and tension relieving dimensions) at different levels of drinking status (i.e. heavy drinking or alcohol dependent groups). To date, no studies have used alcohol administration paradigms to translate neurobiological models of alcoholism etiology to clinical populations. The objective of this application is to examine well-established neurobiological theories of alcoholism etiology in the human laboratory. To do so this study combines traditional alcohol challenge and progressive ratio self-administration methodologies to elucidate the relationship between subjective response to alcohol and one's willingness to work for alcohol. In order to model the transition from positively to negatively reinforced alcohol use two groups (n total = 82) will be recruited, a group of non- dependent heavy drinkers and a group of alcohol dependent individuals. An exploratory aim will examine candidate genes subserving the positive and negative reinforcing effects of alcohol. The proposed study extends the alcoholism literature through testing neurobiologically informed hypotheses about the moderating role of drinking status on subjective response to alcohol in the lab and the relationship between subjective response and self-administration of additional alcohol ad lib.

Public Health Relevance

Alcoholism is a debilitating and costly psychiatric disorder whose neurobiological underpinnings remain poorly understood. Neurobiological models have garnered considerable evidence in preclinical research but have yet to be translated to clinical samples with alcoholism. The proposed research will test neurobiologically-driven hypotheses about subjective response to alcohol and alcohol self-administration in the human laboratory, thus translating animal models of alcoholism neurobiology to clinical samples.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Exploratory/Developmental Grants (R21)
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Health Services Research Review Subcommittee (AA)
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Egli, Mark
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
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Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O et al. (2018) Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm. Neuropsychopharmacology 43:1891-1899
Ray, Lara A; Bujarski, Spencer; Roche, Daniel James Olan et al. (2018) Overcoming the ""Valley of Death"" in Medications Development for Alcohol Use Disorder. Alcohol Clin Exp Res 42:1612-1622
Ray, Lara A; Bujarski, Spencer; Yardley, Megan M et al. (2017) Differences between treatment-seeking and non-treatment-seeking participants in medication studies for alcoholism: do they matter? Am J Drug Alcohol Abuse 43:703-710
Cservenka, Anita; Yardley, Megan M; Ray, Lara A (2017) Review: Pharmacogenetics of alcoholism treatment: Implications of ethnic diversity. Am J Addict 26:516-525
Yardley, Megan M; Ray, Lara A (2017) Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models. Addict Biol 22:581-615
Yardley, Megan M; Mirbaba, Michael M; Ray, Lara A (2015) Pharmacological Options for Smoking Cessation in Heavy-Drinking Smokers. CNS Drugs 29:833-45