The long-range goals of this proposal are to better understand the neurobiological mechanism involved in alcohol relapse. The goals of this application are to (a) better characterized the long-term """"""""Alcohol Deprivation Effect"""""""" (ADE) that develops in some experimental animals following prolonged (1 week or longer) alcohol abstinence and (b) determine if any neuroadaptive changes in certain monamine systems are associated with the ADE. The ADE is described as an enhanced intake of ethanol following a period of alcohol deprivation. The hypothesis to be tested is that, following chronic alcohol drinking and extended abstinence, long-term neuroadaptations, involving alterations in certain serotonin (5-HT) pathways, develop in individuals at risk for alcoholism, which maintain or enhance the rewarding effects of ethanol and contribute to the appearance of the ADE and alcohol relapse. This hypothesis will be tested using adult male alcohol-preferring P rats, which readily demonstrate an ADE following an alcohol deprivation period of one week or longer.
The specific aims will be designed to (1) further characterize the long-term ADE in the P line of rats and determine if a long-term ADE can be produced in the high alcohol-drinking HAD replicate lines of rats, as well as in non-selected Wistar rats; (2) examine whether alterations in the 5-HT3 receptor and/or 5-HT neurotransmission can be found after extended alcohol deprivation in the P rat; and (3) determine, using operant techniques (i.e., progressive-ratio, choice and extinction paradigms), if the reinforcing properties of ethanol are enhanced in the P rats following alcohol abstinence. The results of this proposal will provide information on the neural basis of the ADE. Furthermore, if the ADE observed in animals reflects some aspects of alcohol relapse in humans, then the findings from this application may provide some fundamental knowledge of possible neurobiological factors contributing to alcohol relapse.
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