This project is designed to a) determine the effects of acute and chronic exposure to ethanol (ETOH) on reaction time (reactive capacity); RC in F344 rats of four different ages; b) characterize the development of tolerance to chronic ETOH exposure by experimentally dissociating peripheral metabolic tolerance from behavioral tolerance and by determining the relative role of learning in behavioral (RC) tolerance; c) ascertain the effects of withdrawal on RC, and d) analyze electromyographically (EMG) the acute and chronic effects of ETOH on central (premotor latency) and peripheral (motor time) components of the RC response. The animal model of RC that we have developed over the past 5 years has proven to be very useful in that RC parallels human reaction time in both latency and acquisition characteristics. It is sensitive to aging, ETOH, and other drugs, providing an opportunity to study prolonged and controlled effects of ETOH which could not be accomplished with human subjects. To quantify the acute effects of ETOH on RC, F344 rats aged 4, 12, 20 and 28 mos., previously shaped on the RC task will be tested under conditions of Saline (S), 0.5, 1.0, and 1.5 g/kg ETOH. To distinguish among metabolic (dispositional), cellular (nonlearned, non-metabolic) and learned tolerance, we will compare the performance under acute ETOH challenge (with blood ETOH levels controlled), of rats that have practiced the RC task during ETOH exposure to that of rats that have practiced the RC task while being pair-fed liquid diet or rat chow. The RC of animals of different ages during withdrawal from a 20-day ETOH exposure will be quantified 8, 12, 24, 72 hours and 1 week after termination of the ETOH diet. A particularly unique contribution of this project is the fractionation of the reactive response via EMG in order to determine the effects of both acute and chronic ETOH and aging on central and peripheral components of RC; specifically, effects of ETOH on latencies of agonist-antagonist muscle pairs with respect to the stimulus and to each other will be determined.
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