SELECTIVE BREEDING FOR ETHANOL SENSITIVITY

乙醇敏感性的选择性育种

• 批准号: 6168364
• 负责人: RICHARD A DEITRICH
• 金额: $ 28.42万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-18 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6168364
• 关键词: GABA receptor; alcoholism /alcohol abuse; animal breeding; dehydroepiandrosterone; ethanol; gene expression; genetic mapping; genetic susceptibility; glutamates; laboratory rat; quantitative trait loci; GABA receptor; alcoholism /alcohol abuse; animal breeding; dehydroepiandrosterone; ethanol; gene expression; genetic mapping; genetic susceptibility; glutamates; laboratory rat; quantitative trait loci

DESCRIPTION: (Adapted from the Investigator's Abstract) This proposal utilizes lines of rats that have been selected for differential initial sensitivity to ethanol. These lines will be used to discover which genes control the molecular mechanisms of action of ethanol in the brain. This information will be compared with similar data from mice and the results extrapolated to humans. Identification of genes responsible for the genetic risk of development of alcoholism is the ultimate goal of these studies. These rats, High Alcohol Sensitive, (HAS) and Low Alcohol Sensitive (LAS) and the control lines (CAS) have been selectively bred for 24 generations. The criteria for selection is "sleep time" and blood ethanol at awakening following a standard dose of ethanol. There is essentially no overlap between blood ethanol at awakening between the HAS and LAS lines. Replicate lines, started from separate stocks of the N/Nih heterogeneous stock of rats, are maintained. A Quantitative Trait Loci project is underway and depends upon this proposal for the phenotypic testing of parents, F1 and F2 animals from a cross of both outbred lines and inbred strains. In the current proposal, we undertake to more closely define the actions of ethanol at the GABA receptor and the role of glutamate in the actions of ethanol. We will also investigate very rapid acute tolerance, acute functional tolerance and rapid tolerance. We will investigate the actions of dehydroepiandrosterone and its sulfate derivative on the metabolism and actions of ethanol. Other neurosteroids have been found to have differential effects on ethanol responses in these lines of rats.

描述：（根据调查员的摘要进行了改编）此提案 利用已选择用于差异初始的大鼠线 对乙醇的敏感性。 这些线将用于发现哪些基因 控制乙醇在大脑中作用的分子机制。 这 将信息与小鼠的类似数据和结果进行比较 推断到人类。 识别负责遗传的基因 酗酒的风险是这些研究的最终目标。 这些大鼠对高酒精敏感，（HAS）和低酒精敏感（LAS） 控制线（CAS）已选择性地繁殖了24代。 选择的标准是“睡眠时间”和觉醒时的血乙醇 按照标准剂量的乙醇。 本质上没有重叠 在HAS和LAS线之间觉醒时血液乙醇之间。 复制 线，从N/NIH非均质股票的单独库存开始 大鼠维持。 定量特质基因座项目正在进行中，取决于此提案 对于父母的表型测试，F1和F2动物来自 杂种线和近交菌株。 在当前的提议中，我们承担更紧密的定义 GABA受体的乙醇和谷氨酸在作用中的作用 乙醇。 我们还将研究非常快速的急性耐受性，急性 功能公差和快速公差。 我们将调查行动 在代谢和 乙醇的作用。 已经发现其他神经类似 在这些大鼠这些线中，对乙醇反应的差异影响。