Role of GABA in the locomotor effects of ethanol.

GABA 在乙醇运动效应中的作用。

• 批准号: 7218073
• 负责人: Sarah Elizabeth Holstein
• 金额: $ 4.08万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7218073
• 关键词: GABA receptor; autoradiography; chordate locomotion; dopamine; ethanol; gamma aminobutyrate; high performance liquid chromatography; mesencephalon; microdialysis; muscimol; neurochemistry; pharmacogenetics; predoctoral investigator; synapses

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.

描述（由申请人提供）：FAST和SLOW选择的小鼠品系被培育成对乙醇的运动刺激作用具有高和低敏感性。有证据表明，选择导致了对 GABA-A 受体正调节剂以及 GABA-B 受体激动剂的运动反应的遗传相关系差异。该提议解决了选择改变了 GABA-A 和 GABA-B 受体功能的可能性，特别是在腹侧中脑内，该区域被认为是诱导乙醇运动效应的关键区域。此外，通过微透析测量，该提议解决了选择改变了腹侧中脑内 GABA 突触可用性的可能性，这是一种神经化学事件，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 能对 FAST 小鼠产生运动刺激作用 腹侧中脑的功能，同时通过增加 GABA 能功能诱导 SLOW 小鼠的运动镇静。由于对乙醇刺激作用的急性敏感性被认为是后来成瘾的预测因素，因此阐明这一特征背后的神经生物学和遗传机制非常重要。