GABA-B MODULATION OF ETHANOL-INDUCED LOCOMOTION

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Selected lines are powerful tools in the detection of pleiotropic gene effects. A bidirectional selective breeding program produced the FAST and SLOW selected mouse lines, bred for high and low ethanol-induced locomotor stimulation, respectively. Recent evidence suggests that ethanol's locomotor stimulant effects in FAST mice can be markedly attenuated by the systemic and central administration of baclofen, a selective GABAB receptor agonist. These data suggest that GABAB receptors are involved in the stimulant response to ethanol. This proposal addresses the possibility that genetic selection for the differential ethanol stimulant response altered GABAB receptor density or function, using receptor autoradiography and a GTP-binding functional assay. These data will be used to guide research aimed at identifying the brain site(s) at which GABAB receptors modulate ethanol's locomotor stimulant effects. Site-specific microinjections of baclofen will be used to approach this aim. Because ethanol sensitivity is an important predictor of later alcohol abuse, it is important to understand the determinants of all of ethanol's actions, including stimulation, as they may be relevant to alcohol abuse in humans.