The long range goals of this project are to identify CNS sites, receptors and neurotransmitter systems involved in mediating the rewarding properties of alcohol. The overall hypotheses to be tested in the present proposal are that the posterior ventral tegmental area (VTA) dopamine (DA) neuronal system plays a major role in mediating ethanol (E) reinforcement and there is a relationship between the reinforcing properties of E in the posterior VTA and innate high alcohol drinking behavior. In support of these hypotheses, initial data indicate that Wistar rats will self-administer E directly into the posterior VTA and that self-infusion of E into the VTA is significantly different between lines of rats selectively bred for disparate alcohol drinking behaviors. However, E reinforcement in the VTA has not been fully characterized and it is not known if DA neurons may be mediating E reinforcement within the posterior VTA nor what receptors may be involved. The objectives of this proposal are to 1) characterize the reinforcing properties of E within the VTA of selectively-bred alcohol preferring P, alcohol non-preferring NP, high alcohol-drinking HAD and low alcohol drinking LAD lines of rats, and Wistar rats; 2) establish the involvement of VTA DA neurons and GABA A and 5HT3 receptors in mediating E reinforcement within the posterior VTA; and 3) examine the influence of alcohol drinking on the reinforcing effects of E within the posterior VTA. The technique of intra-cranial self- administration (ICSA) will be used to assess E reinforcement within the VTA. Microdialysis procedures will be used to measure changes in the extracellular levels of DA in the n. accumbens (ACB) as an index of VTA neuronal activity. Pharmacological studies will be undertaken to determine the effects of co-infusing D2, GABAA and 5HT3 receptor agents with alcohol in the posterior VTA on ICSA behavior. The results will establish a relationship between alcohol drinking and the reinforcing effects of E in the posterior VTA and will provide important information on neurotransmitter systems and receptors mediating the reinforcing actions of alcohol, which could be valuable in developing pharmacological strategies for the treatment of alcoholism and alcohol abuse.
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