EXCEED THE SPACE PROVIDED. The long-range goals of this proposal are to better understand the neurobiological mechanismsun- derlying alcohol relapse in individuals at risk for alcoholism.The goals of the present application are to ex- amine neuronal alterations associated with a long-term 'Alcohol Deprivation Effect' (ADE) in rat lines selec- tively bred for high alcohol-seeking characteristics. The overall hypothesis to be tested is that, following chronic ethanol (E) drinking and extended abstinence, neuroadaptations develop and persist in key limbic regions of individuals at risk for alcoholism, which underlie alcohol relapse and contribute to theappear- ance of the ADE. This hypothesis will be tested in the selectively bred alcohol-preferring P and high alco- hol-drinking HAD lines of rats. After a single deprivation period, P rats show a robust ADE, which can be prolonged with repeated deprivations, whereas the HAD lines do not show a robust ADE until afterrepeat- ed deprivations.
The specific aims are designed to examine CMSchangeswhich are produced after chronic E drinking, and following single and repeated long-term deprivations.
Specific aim 1 will usethe intracranial self-administration technique to determine the dose-response effects for self-infusions of E into the post- erior VTA of P and HADrats to examine changes in the reinforcing properties ofE after one or more depri- vations.
Specific aim 2 will use the no-net-flux microdialysis procedure to determine changes in basal dopa- mine (DA) and serotonin (5-HT) neurotransmission in the nucleus accumbens (ACB) after long-term depri- vations. In vivo microdialysis will be used in specific aim 3 to determine changes in the functional activity of 5-HT3 receptors in the ACB of P and HAD rats after long-term deprivations.
Specific aim 4 will use the con- ditioned taste aversion test to determine changes in the threshold to the aversive effects of E after single and repeated deprivations. The results of this application will provide important information on neuralmech- anisms underlying the ADE and neuroadaptationsthat develop following single and multiple long-term deprivations, which contribute to alcohol relapse in individuals at risk for alcoholism. Such information will be importantfor developing pharmacotherapies for the prevention of alcohol relapse. PERFORMANCE SITE ========================================Section End===========================================
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