GABA-B MODULATION OF ETHANOL-INDUCED LOCOMOTION

选择的品系是检测多效性基因效应的有力工具。 双向选择性育种程序产生了FAST和SLOW选择的小鼠品系，分别针对高和低乙醇诱导的运动刺激进行育种。最近的证据表明，酒精的运动刺激作用在FAST小鼠可以显着衰减巴氯芬，选择性GABAB受体激动剂的全身和中央管理。 这些数据表明，GABAB受体参与对乙醇的刺激反应。 这项建议解决了遗传选择的差异乙醇刺激反应改变GABAB受体密度或功能的可能性，使用受体放射自显影和GTP结合功能测定。 这些数据将用于指导旨在确定GABAB受体调节乙醇运动刺激作用的大脑部位的研究。巴氯芬的位点特异性显微注射将用于实现这一目标。 由于乙醇敏感性是后来酒精滥用的一个重要预测因素，因此重要的是要了解乙醇所有作用的决定因素，包括刺激，因为它们可能与人类的酒精滥用有关。

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.