Role of GABA in the locomotor effects of ethanol.

描述（由申请人提供）：饲养FAST和SLOW选择的小鼠品系，以获得对乙醇运动刺激作用的高敏感性和低敏感性。有证据表明，选择导致GABA-A受体阳性调节剂以及GABA-B受体激动剂的运动反应中的遗传相关线差异。该建议解决了选择改变GABA-A和GABA-B受体功能的可能性，特别是在腹侧中脑内，假设该区域是诱导乙醇运动效应的关键。此外，通过微透析测量，这个建议解决了选择已经改变了腹侧中脑内GABA的突触可用性的可能性，神经化学事件可能是乙醇诱导运动活动差异变化的能力的关键。据推测，乙醇可能通过减少GABA能而在FAST小鼠中具有运动刺激作用。 在SLOW小鼠中通过增加GABA能功能诱导运动镇静。由于对乙醇的刺激作用的急性敏感性被认为是后来成瘾的预测因子，因此阐明这一特征背后的神经生物学和遗传机制是很重要的。

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.