Defining the Circuits of Ethanol Response

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DESCRIPTION (provided by applicant): While there is general agreement that no rodent model approximates the uncontrolled consumption of ethanol observed clinically, at least one inbred strain of mice (the C57BL/6J [B6]) shows a high preference and relatively high daily consumption of ethanol (12-20g/kg) compared to most standard inbred mouse strains (e.g. the DBA/2J [D2]). As a first step to understanding the mechanisms associated with excessive alcohol consumption, numerous studies have focused on understanding the differences between the B6 and D2 strains and intercrosses and recombinant inbreds derived from these strains (e.g. Phillips et al. 1994). This application builds from and expands this line of research. We propose to test the hypothesis that the central extended amygdala modulates ethanol preference and consumption; it is further proposed that the dopaminergic innervation to the extended amygdala is central to this modulatory role. Our specific aims areas follows: 1) To in the B6 and D2 strains determine the effects of bilateral electrolytic lesions in the CeA and BSTL on ethanol preference and consumption. 2) To determine in the B6 and D2 strains the effects of Bilateral 6-OH DA lesions in the CeA and BSTL on ethanol preference and consumption. 3) To confirm the marked differences in the pattern of DA innervation in the CeA and BST between the B6 and D2 strains. 4) To characterize the distribution and density of dopamine receptors within the extended amygdala in the B6 and D2 strains. 5) To confirm in animals selectively bred for high and low ethanol consumption, the putative relationships between DA phenotypes (aims 2-4) and ethanol response. 6) To characterize the role of the extended amygdala and the associated DA phenotypes in new models of uncontrolled ethanol consumption developed by the INIA consortium. The experiments associated with each of these aims should provide important new information about the circuits associated with ethanol response and will contribute to the overall goal of the INIA consortium, namely to understand the neurobiology of excessive and uncontrolled ethanol consumption.