The overall objective of the proposed research is to determine the mediate ethanol-motivated behaviors. While alcohol abuse is a problem that receives much research attention, valid animal models of alcohol consumption that address this problem are lacking. The proposed research overcomes this with the use of a novel model that combines a sucrose- substitution procedure to induce high doses of self-administered ethanol, with a runway paradigm that allows for the assessment of motivation to consume ethanol in undrugged non-deprived animals. A series of experiments are proposed to investigate the involvement of the putative dopamine reward system in ethanol-motivated behavior, and the contribution of benzodiazepine systems to ethanol-induced anxiolytic effects. Specifically, rats will be trained to traverse a straight-arm runway for oral access to ethanol/sucrose solutions with progressively increasing ethanol concentrations and decreasing sucrose concentrations. It has already been demonstrated (see Preliminary Data) that this approach can lead to significant ethanol consumption and reliable operant runway responding. Once baseline measures of performance and consumption are stable, changes in runway behavior and ethanol intake will be examined following pretreatment with dopamine and benzodiazepine receptor antagonists. Additionally, intracranial infusions of these drugs will be employed in an attempt to localize the brain sites contributing to motivational and reinforcing effects of self-administered ethanol.
