The primary purpose of this FIRST application is to determine whether there is an association between risk for alcoholism and tolerance and sensitization to ethanol. A multiple-session ethanol administration paradigm is employed to characterize individual differences in chronic tolerance, defined as a decrease in ethanol effects across ethanol exposures, and chronic sensitization, defined as an increase in ethanol effects across ethanol exposures. Males at high and low risk for the development of alcoholism based on family history of this disorder will participate in a nonalcoholic beverage session, and three ethanol sessions in which they consume 1.0 g/kg ethanol. Measures of ethanol's sedative and stimulant effects will be assessed at multiple blood ethanol concentrations on the ascending and descending limbs of the blood ethanol curve. It is hypothesized that tolerance develops to ethanol's sedative effects, whereas sensitization develops to ethanol's stimulant effects. The magnitude of these effects is hypothesized to be greater in men with a family history of alcoholism. In addition, it is predicted that age of alcoholism onset of alcoholic fathers negatively correlates with the magnitude of tolerance to ethanol's sedative effects and sensitization to ethanol's stimulant effects. These effects are also hypothesized to correlate positively with drinking patterns, expectancies about the effects of ethanol, and personality characteristics related to disinhibition. Characterizing individual differences in tolerance and sensitization processes will further our understanding of mechanisms contributing to the initiation and maintenance of heavy ethanol intake. Towards this end, this project will increase knowledge of factors contributing to the etiology of alcoholism.
