GENES REGULATED BY ABUSED DRUGS

受滥用药物调节的基因

• 批准号: 6103868
• 负责人: George Richard Uhl
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6103868
• 关键词: Animalia; amphetamines; antisense nucleic acid; cocaine; drug abuse; drug withdrawal; gene induction /repression; morphine; neuropharmacology; oligonucleotides; protooncogene

Abused drugs produce long-lasting changes in behaviors via biochemical mechanisms that are largely unknown. Drug-altered changes in expression of specific genes in the brain can provide a major window on possible biochemical substrates for addiction. To further explore this area, we have established and developed subtracted differential display and array hybridization techniques that have allowed identification of dozens of distinct cDNAs that correspond to candidate drug-regulated genes expressed in brain. During this FY, we have enhanced characterization of candidate genes whose expression is regulated by amphetamine, cocaine and morphine. Sequence analyses of one of these cDNAs revealed novel splice variant isoforms of a cell adhesion gene family member, NrCAM. Studies of this gene's expression reveal that it is a good candidate to contribute to altered synaptic connectivities that could play roles in the complex neuroadaptive processes characteristic of addiction.

滥用药物会造成长期的变化， 通过生化机制的行为，在很大程度上是未知的。 大脑中特定基因表达的药物改变 可以提供可能的生物化学底物的主要窗口， 成瘾为了进一步探索这一领域，我们建立了 发展的差减显示和阵列杂交技术 这些技术可以识别出几十种不同的 对应于候选药物调节基因的cDNA 在大脑中表达。在本财年，我们加强了 表达受调控的候选基因的表征 安非他明可卡因和吗啡序列分析 这些cDNA揭示了新的剪接变体同种型的细胞 粘附基因家族成员NrCAM。对这种基因的研究 表达表明，它是一个很好的候选人，有助于改变 突触连接在复合体中发挥作用 成瘾的神经适应过程。