Novel Receptor GIR in Amphetamine Sensitization

安非他明致敏中的新型受体 GIR

• 批准号: 6515889
• 负责人: DANZHAO WANG
• 金额: $ 1.04万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6515889
• 关键词: amphetamines; behavioral habituation /sensitization; chemosensitizing agent; complementary DNA; corticosteroid receptors; gene expression; genetic promoter element; genetically modified animals; glucocorticoids; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; messenger RNA; neurons; neurotoxicology; polymerase chain reaction; prefrontal lobe /cortex; protein structure function; receptor expression; tetracyclines; western blottings

DESCRIPTION: (provided by applicant) Behavioral sensitization can be initiated by repetitive stress or stimulant drug administration. Our laboratory has recently cloned and sequenced a glucocorticoid-induced receptor (GIR) cDNA from rat prefrontal cortex in a stress model of learned helplessness. The full-length GIR cDNA encodes a protein belonging to the G protein-coupled receptor superfamily, whose ligand is unknown. This protein shares 31 percent-34 percent amino acid identity to the tackykinin receptors NK-1, NK-2, NK-3. As regulation of neuronal gene expression is hypothesized to be one mechanism by which amphetamine leads to long-term behavioral sensitization, we propose to explore the relationship of GIR to the initiation or maintenance of sensitization. Our preliminary studies demonstrate that chronic amphetamine administration results in elevated expression of GIR in rat prefrontal cortex, which persists long-term (7 days) following drug discontinuing. These findings lead us to hypothesize that modulation of GIR expression may be involved in the physiological regulation and neuroadaptation in the addictive process. This proposal will determine the time-dependent and region-specific expression of GIR in rats sensitized to amphetamine, explore the cellular localization of GIR through in situ hybridization and immunocytochemistry, and generate a transgenic mouse model overexpressing rat GIR.

描述：（申请人提供） 行为敏感化可由重复性压力或刺激物引发 药品监督管理总局.我们的实验室最近克隆并测序了一个 糖皮质激素诱导的受体（GIR）cDNA从大鼠前额皮质， 习得性无助的压力模型。全长GIR cDNA编码一个 属于G蛋白偶联受体超家族的蛋白质，其配体 不明这种蛋白质与其他蛋白质有31%-34%的氨基酸同一性。 粘着激肽受体NK-1、NK-2、NK-3。作为神经元基因的调控 表达被假设为安非他明导致 长期的行为敏化，我们建议探索的关系， GIR启动或维持致敏作用。我们的初步研究 表明慢性安非他明给药导致 大鼠前额叶皮质中GIR的表达，持续时间长（7天） 药物停止后。这些发现让我们假设， GIR表达的调节可能参与了细胞的生理调节 以及成瘾过程中的神经适应。该提案将决定 致敏大鼠GIR表达的时间依赖性和区域特异性 苯丙胺，通过原位杂交探讨GIR的细胞定位 杂交和免疫细胞化学，并建立转基因小鼠模型 过表达大鼠GIR。