Indiana Genetic Animal Models Core

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DESCRIPTION (provided by applicant): The long-term objective of this research is to investigate neuroadaptations within the extended amygdala and its interconnections following excessive ethanol consumption in rats. One series of experiments will ensure the quality control and availabity of rats taken through the excessive ethanol drinking animal model. Towards this end, high-alcohol-consuming P and HAD (both replicate lines) rats will be taken through an ethanol drinking protocol involving repeated cycles of exposure to multiple ethanol concentrations followed by a period of deprivation. A second series of experiments will further characterize and refine the ethanol drinking protocol by evaluating the effects of altering the length of initial and subsequent 1) ethanol exposures and 2) deprivations and changing the available ethanol concentrations. A third series of experiments will examine the influence this experimental paradigm of cycles of ethanol availability and deprivation has in the drinking pattern of low-alcohol-consuming (e.g., NP, LAD-1, LAD-2 and Wistar) rats. The ethanol drinking protocol results in very high levels of ethanol intake in P and HAD rats (up to 16g/kg/day on the reinstatement of multiple concentrations of ethanol after three cycles of exposure and deprivation), suggesting that the reinforcing properties of ethanol may have been enhanced. The main hypothesis to be tested is that experience with excessive ethanol drinking results in neuroadaptive alterations in the extended amygdala and its interconnections. The rat lines that have been genetically selected for high alcohol drinking at Indiana University (i.e., P, HAD-1 and HAD-2) have been known to exhibit "loss of control" drinking when exposed to the ethanol drinking protocol proposed in this program. The results of this proposal will provide valuable information toward understanding the neural circuitry underlying excessive alcohol drinking and relapse of alcohol drinking. Such information would be important for developing pharmacotherapies for the treatment of alcoholism and alcohol abuse.