Mechanisms of Alcohol Tolerance and Priming in Humans

University Of Kentucky, Lexington KY

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Abstract

DESCRIPTION (provided by applicant): Excessive alcohol use (i.e., a binge) contributes to many adverse health consequences (e.g., alcohol poisoning, acute alcoholic hepatitis and live cirrhosis). Alcohol is well-known for its acute impairing effects on neurocognitive processes involved in the regulation of behavior and attention. Yet, little research has examined how such disturbances might reduce self-control over actual alcohol use, leading to patterns of abusive drinking (e.g., binge drinking). Given that even mild doses of alcohol impair control of behavior and attention, it is important to understand how acute intoxication can reduce control over alcohol intake once a drinking episode has begun. The proposed project is based on the hypothesis that abuse potential of alcohol is determined by its reward-enhancing effects and its disruptive effects on control mechanisms. Experiments will examine non-dependent adults and will test the disruptive effects of alcohol on neurocognitive control mechanisms in relation to two characteristics associated with increased alcohol abuse: 1) alcohol-induced priming of self-administration;2) the development of alcohol tolerance. Studies examine the effects of controlled doses of alcohol on neurocognitive performance tasks that measure inhibitory and activational aspects of control. The measures will be studied in relation to alcohol-induced priming of self-administration and in the development of learned alcohol tolerance. The findings will provide an understanding of how drinkers'susceptibility to alcohol's acute behavioral-impairing effects can pose an early-onset risk factor for later alcohol dependence by promoting a continued pattern of abusive binge drinking. The research strategies also will provide methods for testing the role of neurocognitive mechanisms in the treatment efficacy of existing pharmacotherapies, such as naltrexone and acamprosate, as well as some investigational medications that might operate via neurocognitive control mechanisms: