BRAIN DIALYSIS AND ETHANOL SELF-ADMINISTRATION

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The present proposal is designed to extend previous work in this laboratory aimed at identifying neuronal circuitries and neurochemical substrates involved in ethanol reward and dependence. It is the purpose of this project to use the intracranial microdialysis technique to monitor the synaptic concentration of several forebrain transmitters previously implicated in ethanol seeking behavior and reward, and to establish a "profile" of basal and ethanol-induced neurotransmitter activity for both unselected Wistar and alcohol-preferring (P-1) rats. Transmitter release will be monitored before and during oral ethanol self-administration in a two-lever free-choice (water/ethanol 10%w/v) condition, using dependent rats undergoing ethanol withdrawal. Additionally, high and low responders for ethanol intake. Dialysate will be collected from the nucleus accumbens, caudate nucleus and ventral pallidum, and will be assayed for dopamine (DA), 5-hydroxytryptamine (5- HT) or gamma-aminobutyric acid (GABA). These data will serve to identify differences in basal DA, 5-HT and GABA levels between two strains of rats differing in their preference for ethanol, establish the neurochemical effects of self-administered ethanol on the release of these transmitters, and will help determine their role in ethanol reward and dependence. Finally, the effects of ethanol on neurotransmitter activity will be compared to those of other drugs of abuse including cocaine and heroin, These studies have important implications with regard to the understanding of ethanol actions on central neurotransmitter systems and the identification of neural substrates for ethanol reward. Such issues are of critical importance for the development of effective strategies for the prevention and treatment of ethanol abuse and dependence.