GABA-B MODULATION OF ETHANOL-INDUCED LOCOMOTION

选育的品系是检测多效性基因效应的有力工具。双向选择育种计划产生了快速和缓慢选择的小鼠品系，分别为高和低乙醇诱导的运动刺激而培育。最近的证据表明，乙醇对快速小鼠的运动刺激作用可以通过全身和中枢给予选择性GABAB受体激动剂巴氯芬而显著减弱。这些数据表明，GABAB受体参与了对乙醇的刺激反应。这项建议利用受体放射自显影和GTP结合功能分析，解决了对不同乙醇刺激反应的遗传选择改变GABAB受体密度或功能的可能性。这些数据将用于指导旨在确定GAAB受体调节乙醇运动刺激效应的大脑部位(S)的研究。将使用特定部位的巴氯芬微量注射来实现这一目标。由于乙醇敏感性是未来酗酒的一个重要预测因素，因此了解包括刺激在内的所有乙醇行为的决定因素是很重要的，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.