Defining the Circuits of Ethanol Response

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.