The rationale of this study is to understand the mechanims underlying kappa opioid receptor (KOR) mediated stress-induced potentiation of cocaine conditioned place preference (CPP) from a signal transduction and anatomical perspective. This research proposal will examine the molecular and physiological mechanisms underlying the KOR-mediated stress response. Preliminary results suggest that this response is mediated by KOR-induced MAPK activation. Using striatal brain region homogenates, we will examine how stress (modified forced swim) changes reward circuitry in a KOR-dependent fashion. This proposed study will assess the role of G-protein coupled receptor kinase (GRK3) shown in preliminary studies to be necessary for the KOR-mediated stress response. In addition, these studies will examine the cell types and neuronal populations that these stress-induced KOR-mediated events occur by using antibodies specific for the the phosphorylated KOR (activated), MAPKs and neuronal markers. In doing so we will use tissue immunohistochemistry and primary culture techniques to understand the spatial and temporal relationship of KOR-mediated signal transduction following stress.
