The primary aim of the revised application is to understand cognitive features and brain systems that differentiate low- and high-level responders to alcohol, while under the influence of alcohol and without alcohol intoxication. Participants will be young adults ages 18-25 with the following exclusions: history of substance dependence or major psychiatric disorder, medical illness or use of medications that might interfere with alcohol challenge or affect brain imaging results, pregnancy, have had unpleasant reactions to moderate alcohol doses, left handed, or magnetic resonance imaging contraindications (e.g., metal, claustrophobia). Participants will be selected from annual mailings to college students, and classified as low or high level responders to alcohol, initially based on a standardized self-report instrument. Potential participants will receive a detailed diagnostic interview, and a traditional alcohol challenge to confirm level of response to alcohol and comfort in consuming moderate doses. Low (n=50) and high (n=50) level responders will be matched on: height, weight, race, gender, and recent use of alcohol, nicotine, and other drugs. Eligible participants will receive functional magnetic resonance imaging (fMRI) two times: after drinking moderate doses of alcohol (up to 0.68 ml/kg alcohol for women and up to 0.75 ml/kg alcohol for men) and after drinking placebo. Order of beverage administration will be randomized. Each fMRI assessment will administer Visual Working Memory and Sensorimotor tasks during blood oxygen level dependent scan acquisition, structural MRI (for spatial localization), and arterial spin labeling (to control blood flow differences). The imaging session will start 30 minutes after beverage administration and last one hour, recording results at rising and falling BACs. The two imaging sessions will occur within the same week. Data will be compared in 2x2 analyses of variance to compare brain activation between low and high level responders with and without alcohol intoxication. These results will potentially develop a method for identifying low responders (a group at high risk for alcoholism) even before their first drink. The project will also expand our understanding of the neural substrates of the level of response to alcohol, a key risk factor for the development of alcohol dependence.
