Stress-related neuropeptides and VTA dopamine neurons

压力相关神经肽和 VTA 多巴胺神经元

• 批准号: 7111941
• 负责人: Matthew J. Wanat
• 金额: $ 3.24万
• 依托单位: ERNEST GALLO CLINIC AND RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111941
• 关键词: dopamine; emotions; neurons; neuropeptides; stress

DESCRIPTION (provided by applicant): One major problem involved with treating drug addiction is the high incidence of relapse to drug taking, which often is triggered by stressful events. Stress induces the release of dopamine, and the increased levels of dopamine are required for relapse to drug seeking. Thus, preventing stress-induced dopamine release may have therapeutic implications in reducing the incidence of relapse. The proposed research studies how stress affects dopamine-producing cells in order to identify targets which could prevent stress- induced dopamine release. Stress induces the release of corticotropin-releasing factor (CRF) and substance P (SP) onto dopamine cells. The aims of this proposal are to identify the mechanisms by which CRF and SP affect the firing of dopamine cells. Specifically, this project will determine the receptors, the intracellular signaling pathways, and the currents that are altered by CRF and SP. Potential therapeutic targets for reducing the incidence of stress-induced relapse will be identified through determining the mechanism through which SP and CRF act on dopamine neurons.

描述（由申请人提供）：治疗药物成瘾的一个主要问题是药物复发的高发生率，这通常是由压力事件引发的。压力诱导多巴胺的释放，而多巴胺水平的增加是药物寻求复发所必需的。因此，防止应激诱导的多巴胺释放可能对减少复发率具有治疗意义。本研究旨在研究应激对多巴胺产生细胞的影响，以确定能够阻止应激诱导的多巴胺释放的靶点。应激诱导促肾上腺皮质激素释放因子（CRF）和P物质（SP）向多巴胺细胞释放。本建议的目的是确定CRF和SP影响多巴胺细胞放电的机制。具体来说，该项目将确定受体、细胞内信号通路以及被CRF和SP改变的电流。通过确定SP和CRF作用于多巴胺神经元的机制，将确定减少应激诱导复发发生率的潜在治疗靶点。