Role of GABA in the locomotor effects of ethanol.

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DESCRIPTION (provided by applicant): The FAST and SLOW selected mouse lines were bred for high and low sensitivity to the locomotor stimulant effects of ethanol. Evidence suggests that selection has resulted in genetically correlated line differences in the locomotor response to GABA-A receptor positive modulators, as well as to a GABA-B receptor agonist. This proposal addresses the possibility that selection has altered GABA-A and GABA-B receptor function, specifically within the ventral midbrain, an area hypothesized to be key to the induction of the locomotor effects of ethanol. In addition, as measured through microdialysis, this proposal addresses the possibility that selection has altered the synaptic availability of GABA within the ventral midbrain, a neurochemical event that may be key to the ability of ethanol to induce differential changes in locomotor activity. It is hypothesized that ethanol may be having its locomotor stimulant effects in FAST mice through decreased GABAergic function in the ventral midbrain, while inducing locomotor sedation in SLOW mice through increased GABAergic function. As acute sensitivity to ethanol's stimulant effects is suggested to be a predictor of later addiction, it is important to elucidate the neurobiological and genetic mechanisms underlying this trait.