Cognitive Mechanisms of Alcohol Abuse

Excessive alcohol use during a drinking episode (i.e., a binge) contributes to many adverse health and social consequences. Binge drinkers are more likely to drive while intoxicated and to suffer blackouts and hangover. A continued pattern of binge drinking poses immediate health risks (e.g., alcohol poisoning, acute alcoholic hepatitis), and long-term consequences, such as alcohol dependence and liver cirrhosis. Given that even mild doses of alcohol impair cognitive processes that control behavior, it is important to understand how such disturbances also can reduce control over alcohol intake once a drinking episode has begun. The proposed project aims to determine how the inability to curtail alcohol consumption during a drinking episode is linked to alcohol-induced impairment of cognitive processes involved in the self-control and regulation of behavior. The research will examine acute alcohol impairment of cognitive functions in young non-dependent drinkers. The project combines measures of alcohol effects on cognitive inhibitory processes with traditional abuse liability indices based on subjective rewarding effects of the drug and its ability to reinforce self-administration. Studies will determine the degree to which alcohol abuse potential is influenced by two mechanisms of drug action: 1) reward-enhancing effects (i.e., elevation of an approach "go" mechanism); and 2) impairment of cognitive inhibitory processes (i.e., suppression of an avoidance "stop" mechanism). Multiple strategies will test the role of acute cognitive impairment in the abuse liability of alcohol. A drug-reinforcement model will test the degree to which preload alcohol doses "prime" subsequent drug self-administration by impairing inhibitory control processes that regulate behavior. The research also will test an indirect alcohol antagonist drug. caffeine, and an approved medication for alcohol abuse, naltrexone, for their ability to reduce alcohol self-administration by blocking its impairing effects on inhibitory control. The research has several long-term objectives. The findings will provide an understanding of how drinkers' susceptibility to alcohol's acute cognitive-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 cognitive mechanisms in the treatment efficacy of existing pharmacotherapies. such as naltrexone, as well as some investigational medications that might operate via cognitive mechanisms (e.g., acamprosate). Finally, the proposed experiments will provide initial methods and protocols for studying alcohol use in combination with other drugs of abuse that also disrupt cognitive functions, such as cocaine, for which binge use is also a common pattern of drug-taking.