Functional magnetic resonance imaging (fMRI) has only recently begun to identify specific brain regions where responses to stimuli associated with dnnking ("alcohol cues") vary as a function of a family history of alcoholism (Kareken et al., 2010a;Tapert et al., 2003). The long-term goal of our research is to determine how alcoholism risk factors alter the brain's reward system function. The objective of this application is to determine how genetic, behavioral, and personality trait risks alter the brain's processing of cues that have been classically conditioned to predict imminent intoxication in the experimental setting. Our rationale is that, by carefully controlling learning and contingencies in the laboratory, we can better measure brain responses to alcohol predictive cues, and do so with cues devoid of the influence from prior idiosyncratic alcohol experiences. The central hypothesis of these studies is that brain responses to cued alcohol intoxication will differ as a function of both genetic and behavioral risk factors. By identifying the brain systems affected by family history, behavioral disorders, and specific genes, we will gain a more complete understanding of the nsk pathways and associated neural vulnerabilities that help lead to alcoholism. Using fMRI, we will test three specific aims: 1) Test whether a family history of alcoholism alters brain responses to novel cues experimentally paired with the ascending limb of the blood alcohol curve. 2) Test whether brain responses to experimentally conditioned cues are modified by the presence of high externalizing behaviors. 3) Test whether GABRA2 variation affects local brain responses to cues experimentally conditioned to intoxication.
Our proposed research will identify how alcoholism risk factors are reflected by brain responses that encode the anticipation of impending alcohol intoxication and how the human brain learns about stimuli (sensations) that predict imminent intoxication-- stimuli that can eventually increase alcohol cravings and impel individuals to seek alcohol.
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