Cholinergic modulation of ethanol-induced stimulation

描述(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。事实证明，使用这些简单的行为或内表型有助于理解药物滥用和成瘾。其中一种行为是对药物的运动刺激。目前的证据表明，9号染色体上有一个共同的基因或数量性状基因(QTL)影响对可卡因、乙醇和甲基苯丙胺的敏感性。这个QTL将被一个9号染色体C57BL/6J区域导入DBA/2J背景的同源小鼠品系所证实。烟碱型乙酰胆碱(NACH)受体在药物刺激中的作用将通过药理学和分子技术进行研究。具体地说，包含A3亚单位的NACH受体的作用将被研究，因为这代表了一个潜在的候选基因，位于9号染色体的QTL区域。除了受体拮抗剂的研究外，定量逆转录聚合酶链式反应将用于检测mRNA的表达，放射自显影将用于检测受体密度的差异。这些数据将为NACH受体参与药物诱导的刺激以及药物的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.