IDENTIFICATION OF GENES INVOLVED IN NEURAL SIGNALLING

滥用药物-诱发长期的行为障碍，被认为是 由中枢神经系统中的生物机制维持， 大部分都是未知的。 在前几个财政年度， 开发了识别这些基因的方法，并记录了候选基因 受滥用药物调控的基因，包括 安非他明可卡因和吗啡 几个基因可以很容易地 被认为是神经元信号传导的可能参与者， 鉴定 这些基因包括编码一种新的G蛋白β的基因 亚基，编码主要调节脑磷蛋白的基因 磷酸酶，钙调神经磷酸酶，和一个新的G蛋白连接的编码基因， 受体的 G-β表达的功能意义是通过使用 在神经母细胞瘤细胞中的正义和反义过表达，以及在体内 在脑室内注射到实验动物中后。 初始 结果揭示了对体外神经突起生长的影响， 可卡因在体内诱导的致敏作用与 这种G蛋白在神经适应中可能扮演的有趣角色 这是由滥用药物引起的。

Abused drugs-induce long-term behavioral disorders that are thought to be maintained by biological mechanisms in the central nervous system that are largely unknown. Work in this group during previous FYs has developed approaches to identify such genes and documented candidate genes whose expression are regulated by abused drugs, including amphetamine, cocaine and morphine. Several genes that can be readily identified as possible participants in neuronal signalling have been identified. These genes include that encoding a novel G protein beta subunit, a gene encoding a major regulated brain phosphoprotein phosphatase, calcineurin, and a gene encoding a novel G-protein-linked receptor. Functional implications of G-beta expression were sought using sense and antisense overexpression in neuroblastoma cells, and in vivo following intraventricular injection into experimental animals. Initial results reveal effects on neural process outgrowth in vitro and on cocaine-induced sensitization in vivo that are consistent with interesting possible roles for this G protein in the neuroadaptations that result from abused drug administration.