GENES REGULATED BY ABUSED DRUGS IN BRAIN--GENES INVOLVED IN NEURAL SIGNALING

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 大部分是未知的。 在前几个财政年度， 开发了一种方法来识别这些基因，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 在本财政年度， 更多基因的调控已被表征， 使用G-beta和c-fos过度表达的影响 脑室和脑内注射反义核酸 寡核苷酸抗G β寡核苷酸，其有效抑制 降低G β免疫反应性水平能够阻断 可卡因诱导的致敏作用，但在阻断 当它们在下列情况下给药时， 致敏剂量 这些影响在几周内是可逆的。 脑内注射抗cfos反义寡核苷酸也 逆转可卡因戒断的一些特征。 这些结果 支持的可能性，一些产品的基因确定为 急性和慢性给药的上调或下调可能 在成瘾现象中起作用。

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 a approaches to identifying 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. During this FY, the localized expression and functional regulation of more genes have been characterized and the functional implications of G-beta and cfos overexpression documented using intraventricular and intracerebral injection of antisense oligonucleotides. AntiGbeta oligonucleotides that are effective iin reducing levels of Gbeta immunoreactivity are able to block establishment of cocaine-induced sensitization, but are ineffective in blocking the expression of sensitization when they are administered following sensitizing doses. Theses effects are reversible over several weeks. Intracerebral injections of anti-cfos antisense oligonucleotides also reverse some of the features of cocaine withdrawal. These results support the likelihood that some of the products of genes identified as up- or downregulated by acute and chronic administration are likely to play roles in addictive phenomena.