Cholinergic modulation of ethanol-induced stimulation

乙醇诱导刺激的胆碱能调节

• 批准号: 6991746
• 负责人: Helen M Kamens
• 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/6991746
• 关键词: autoradiography; drug abuse; ethanol; gene expression; messenger RNA; neuropharmacology; neuroregulation; nicotinic receptors; polymerase chain reaction; predoctoral investigator; quantitative trait loci; receptor expression

DESCRIPTION (provided by applicant): One way to study the biological underpinnings of complex traits is to make use of simple behaviors that can predict complex traits. The use of these simple behaviors, or endophenotypes, are proving useful in understanding drug abuse and addiction. One such behavior is locomotor stimulation in response to a drug. Current evidence suggests that there is a common gene or quantitative trait locus (QTL) on chromosome 9 that influences sensitivity to cocaine, ethanol, and methamphetamine. This QTL will be confirmed with a congenic mouse strain that has a C57BL/6J region of chromosome 9 introgressed on a DBA/2J background. The role of nicotinic acetylcholine (nACh) receptors in drug induced stimulation will then be examined by using pharmacologic and molecular techniques. Specifically, the role of nACh receptors containing an a3 subunit will be examined because this represents one potential candidate gene that resides in the chromosome 9 QTL region. In addition to receptor antagonist studies, quantitative reverse transcriptasepolymerase chain reaction will be employed to examine mRNA expression and autoradiography will be used to examine receptor density differences. These data will provide evidence for the involvement of nACh receptors in drug-induced stimulation and in drug use and abuse.

描述（由申请人提供）：研究复杂性状的生物学基础的一种方法是利用可以预测复杂性状的简单行为。使用这些简单的行为，或内表型，在理解药物滥用和成瘾方面被证明是有用的。其中一种行为是对药物反应的运动刺激。目前的证据表明，在9号染色体上有一个共同的基因或数量性状位点（QTL）影响对可卡因、乙醇和甲基苯丙胺的敏感性。该QTL将在一个具有DBA/2J背景的9号染色体C57BL/6J区域渗入的小鼠基因株中得到证实。烟碱乙酰胆碱（nACh）受体在药物诱导刺激中的作用将通过药理学和分子技术进行研究。具体来说，包含a3亚基的nACh受体的作用将被研究，因为这代表了位于9号染色体QTL区域的一个潜在的候选基因。除了受体拮抗剂研究外，定量逆转录聚合酶链反应将用于检查mRNA表达，放射自显影将用于检查受体密度差异。这些数据将为nACh受体参与药物诱导刺激和药物使用和滥用提供证据。