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.