Alcoholism is marked by profound sleep disturbances. The clinical observation that sleep disturbances are related to the course of the disease has been confirmed by a number of studies. Although many of the abnormalities of the alcoholic sleep syndrome abate with abstinence, there is still a disorganization of the normal circadian rhythms of sleep after more than a year without drinking. We have shown that ethanol selection, in amounts readily chosen by C57BL/6J mice, is associated with a slowing of the circadian rhythm of drinking in constant dark. This slowing of biological timing may be the basis of the circadian disruptions found in the human disease of alcoholism. It is our objective in the work proposed to further define the role of alcohol in the disorganization of circadian rhythms. Specific issues to be addressed are: whether voluntary alcohol consumption in the mouse disrupts the normal circadian synchrony of eating, drinking and locomotor activity rhythms; the possible disruption of circadian timing consequent to abrupt withdrawal in mice after prolonged voluntary alcohol consumption; the effect of voluntary ethanol consumption on the mouse's ability to reentrain to altered light-dark cycles; the phase-response curve for the 'clock resetting' effect of alcohol; the relationship of different individual patterns of voluntary alcohol consumption to the magnitude of circadian timing changes induced; and the importance of voluntary alcohol consumption, compared to forced ethanol intake, in their disruptive effect on the circadian timing system. Continuous monitoring, on an individual basis, of groups of C57BL/6J mice by calibrated lickometers and microcomputers for data acquisition, storage and retrieval will be used at two levels of temporal resolution--hourly counts and six-minute counts--with tallies of interlick intervals. Feeding and wheel-running will be studied in like manner. All experiments will begin with a six-week baseline in 12-12 hour light-dark condition for comparability across protocols. The program of research outlined here is proposed as a model system in the mouse for the study of ethanol's effects on the temporal organization of biological function.
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