Stress-related neuropeptides and VTA dopamine neurons

描述(申请人提供)：与治疗毒瘾有关的一个主要问题是吸毒复发的高发生率，这通常是由应激性事件引发的。压力会导致多巴胺的释放，而多巴胺水平的增加是吸毒复发所必需的。因此，防止应激诱导的多巴胺释放可能在减少复发方面具有治疗意义。这项拟议的研究研究了压力如何影响多巴胺产生细胞，以确定可以防止压力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)释放到多巴胺细胞。这项建议的目的是确定CRF和SP影响多巴胺细胞放电的机制。具体地说，该项目将确定CRF和SP改变的受体、细胞内信号通路和电流。通过确定SP和CRF对多巴胺神经元的作用机制，将确定减少应激诱导复发的潜在治疗靶点。

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.