Mechanisms of activation of nucleus accumbens neurons by cocaine via sigma-1 receptor-inositol 1,4,5-trisphosphate-transient receptor potential canonical channel pathways

- Cocaine enhances IP3-mediated Ca2+ signaling via sigma-1-receptor (σ1R).
- This induces TRP canonical (TRPC) activation and depolarization of accumbal neurons.
- Intra-accumbal σ1R/TRPC blockade reduces cocaine-hyperlocomotion/sensitization.
- We show behavioral relevance of a novel cocaine-triggered pathway in the accumbens.