Several converging lines of evidence link alcohol intake to circadian biological rhythms in both humans and experimental animals. Thus, voluntary alcohol intake and alcohol sensitivity are modulated by time-of-day (circadian phase), while alcohol consumption and alcohol withdrawal alter sleep and circadian rhythms, in both humans and experimental animals. Indeed, it is likely that alcohol-induced alterations in sleep and circadian rhythmicity contribute to the negative health consequences of excessive alcohol consumption and alcoholism. Nevertheless, a major shortcoming of chronobiological research on alcohol till now has been the failure to determine whether alcohol-induced disruptions of sleep and circadian rhythms are mediated by pharmacologic effects of alcohol on the underlying circadian pacemaker. In addition, previous animal research on the chronobiology of alcohol has failed to utilize well-validated animal models of human alcoholism. The studies presented in this proposal have been designed explicitly to address these shortcomings in the existing literature. Specifically, these studies will (1) examine relationships between genetically-based alcohol preference and circadian rhythms in selectively-bred alcohol preferring and alcohol-non-preferring rats, prior to experience with alcohol drinking, (2) characterize the chronobiological effects of excessive alcoholic-like drinking in alcohol-preferring rats subjected to repeated periods of alcohol access and alcohol withdrawal, thus simulating the effects of repeated relapse in human alcoholics, (3) explore the ability of both acute and chronic alcohol treatments to affect the circadian pacemaker in Syrian hamsters, an important animal model in chronobiological research due to its highly precise activity rhythm, and (4) identify the possible role of a specific alcohol-sensitive neurotransmitter receptor, the GABA-A receptor, in mediating the pharmacologic effects of alcohol on the circadian pacemaker. The results of these studies will contribute substantially to understanding both the causes and the consequences of sleep and circadian rhythm disruptions occurring in human alcoholics.
