The goals of the proposed research are to determine the protective effects of exercise against acute and chronic ethanol (EtOH) intoxication and EtOH withdrawal in C57BL/6J and BALB/cByJ mice, and to provide preliminary information on the possible mechanisms of these effects. The proposed research would provide the first systematic study of prior exercise on multiple indices of EtOH sensitivity, including activity, avoidance behavior, body temperature, and loss of righting response. These differing EtOH sensitivities in mice presumably model genetic components of EtOH response in humans and as such have implications for the effects of exercise on human EtOH response. Preliminary work has established that five weeks of voluntary wheel running given before EtOH challenge causes significant resistance to EtOH-induced behavioral intoxication, i.e., less suppression of activity and less impairment on an avoidance task after 2.4 g/kg EtOH (20% w/v, IP), and also causes significant resistance to EtOH- induced hypothermia and Loss of Righting response (LORR) after 3.8 g/kg EtOH (20% w/v, IP). New pilot data are suggestive of the possibility that these protective effects of exercise are sustained over a 24-hour exercise- free period. The objectives of the proposed research are to determine 1) the extent to which the protective effects of exercise against EtOH intoxication, including behavioral impairment, LORR and hypothermia, can be sustained over exercise-free periods of 24 hours and 1 week, thus, ruling out acute metabolic factors, 2) the effectiveness and possible """"""""dose effects"""""""" of limited exercise, 2 hours of wheel access per day versus continuous access, 3) the extent to which exercise can attenuate the severity of withdrawal symptoms following termination of chronic EtOH administered in the diet, and 4) the extent to which the protective effects of exercise against EtOH intoxication can be achieved in animals that have developed EtOH tolerance through EtOH administered in the diet. Preliminary information on mechanisms of these effects will be obtained by assessing effects of prior exercise on 1) body composition (body water determined by desiccation), 2) blood EtOH concentration (BEC) at regaining of the righting response (RORR), and 3) EtOH clearance rate relative to the time course of EtOH-induced hypothermia. Since much of the alcohol-related cost to society results directly from behavioral impairment due to intoxication, elucidation of mechanisms by which exercise might mitigate these effects could in the long term have important implications for human health and welfare. On the basis of pilot work the contribution of dispositional factors is expected to be minimal. An extensive literature on EtOH tolerance has now documented a number of neurocellular systems that are modified by continued EtOH exposure. These modifiable systems are logical candidates for mediation of exercise effects on EtOH response and would be the focus of future research.
