Novel Receptor GIR in Amphetamine Sensitization

安非他明致敏中的新型受体 GIR

• 批准号: 6340439
• 负责人: DANZHAO WANG
• 金额: $ 4.94万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6340439
• 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） 行为敏化可以通过重复应力或兴奋剂引发 药物管理局。我们的实验室最近克隆并测序了 糖皮质激素诱导的受体（GIR）cDNA来自大鼠前额叶皮层 学习无助的压力模型。全长GIR cDNA编码A 属于G蛋白偶联受体超家族的蛋白质，其配体 是未知的。该蛋白具有31％-34％的氨基酸身份 毒素受体NK-1，NK-2，NK-3。作为神经元基因的调节 表达被认为是苯丙胺导致的一种机制 长期行为敏感，我们建议探索 GIR开始或维持致敏。我们的初步研究 证明慢性苯丙胺给药会导致升高 GIR在大鼠前额叶皮层中的表达，长期持续（7天） 停药后。这些发现使我们假设 GIR表达的调节可能与生理调节有关 和上瘾过程中的神经适应。该建议将确定 GIR在大鼠中的时间依赖和区域特异性表达 苯丙胺，探索GIR通过原位的细胞定位 杂交和免疫细胞化学，并生成转基因小鼠模型 过表达的大鼠GIR。