Cholinergic modulation of ethanol-induced stimulation

描述（由申请人提供）：研究复杂特征的生物学基础的一种方法是利用可以预测复杂特征的简单行为。使用这些简单的行为，或内表型，被证明是有用的，在理解药物滥用和成瘾。一种这样的行为是响应于药物的运动刺激。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将用具有在DBA/2 J背景上渗入的9号染色体的C57 BL/6 J区域的同类小鼠品系来确认。烟碱乙酰胆碱（nACh）受体在药物诱导的刺激中的作用，然后将通过使用药理学和分子技术进行检查。具体而言，将检查含有α 3亚基的nACh受体的作用，因为这代表了位于9号染色体QTL区域中的一个潜在候选基因。除了受体拮抗剂研究，定量逆转录聚合酶链反应将被用来检查mRNA表达和放射自显影将被用来检查受体密度差异。这些数据将为nACh受体参与药物诱导的刺激以及药物使用和滥用提供证据。

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.