SEROTONIN MECHANISMS IN ETHANOL AND THERMOREGULATION

乙醇中的血清素机制和体温调节

• 批准号: 6070069
• 负责人: KAITLIN E. BROWMAN
• 金额: $ 1.45万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-11 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6070069
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; autoradiography; behavioral /social science research tag; behavioral genetics; body temperature regulation; ethanol; gene interaction; gene targeting; genetic models; genetic susceptibility; genetically modified animals; in situ hybridization; induced hypothermia; laboratory mouse; messenger RNA; mutant; neurotransmitter agonist; receptor expression; serotonin receptor

To help elucidate the complex gene interactions thought to underlie the neural effects of alcohol, our research group has instituted a replicated bidirectional selective breeding program which has produced the HOT and COLD lines of mice, bred for differing sensitivity to the hypothermic effect of ethanol. Thermoregulation provides a useful and interesting system for investigating sensitivity to ethanol. Although it is clear that the serotonergic neurotransmitter system is involved in mediating differences in ethanol-induced hypothermia between the HOT and COLD selected lines, the mechanism (e.g., the specific receptor subtype involved) is less clear. Recent research implicates the serotonin 1B (5-HT1B) receptor in mediating several ethanol induced effects, including hypothermia. To specifically address the role of the serotonin 5-HT1B receptor in mediating ethanol-induced hypothermia, this proposal will study ethanol- induced hypothermia in HOT and COLD mice, as well as null mutants for the serotonin 5-HT1B receptor. These experiments will increase our understanding of genetic factors mediating ethanol's effects, and could help in developing pharmacotherapies for alcohol abuse.

为了帮助阐明认为是为了构成酒精神经作用的复杂基因相互作用，我们的研究小组提出了一个复制的双向选择性育种程序，该计划产生了小鼠的热和冷线，繁殖出对乙醇低温作用的敏感性。温度调节为研究对乙醇的敏感性提供了一个有用且有趣的系统。 尽管很明显，血清素能神经递质系统参与介导乙醇诱导的热和冷选择线之间的体温过低的差异，但该机制（例如，涉及的特定受体亚型）尚不清楚。 最近的研究暗示5-羟色胺1b（5-HT1B）受体介导了几种乙醇诱导的作用，包括体温过低。 为了特别解决5-羟色胺5-HT1B受体在介导乙醇诱导的体温过低中的作用，该建议将研究热和冷小鼠中乙醇诱导的体温过低，以及5-羟色胺5-HT1B受体的无效突变体。 这些实验将增加我们对介导乙醇作用的遗传因素的理解，并可能有助于开发用于酗酒的药物治疗。