Transient Receptor Potential Vanilloid Type I Channel May Modulate Opioid Reward

Transient receptor potential vanilloid type 1 (TRPVI), a nonselective cation channel, is a well-known pain-related receptor. TRPVI involvement in morphine-induced antinociception, tolerance, and withdrawal symptoms has been previously reported. Emerging evidence indicates that TRPVI may be related to both the cellular and behavioral effects of addictive drugs. In the present study, we investigated the role of TRPVI in morphine reward using the conditioned place preference (CPP) paradigm in mice. Repeated morphine treatments upregulated TRPVI expression in the dorsal striatum (DSt). Treatment with a TRPVI agonist potentiated morphine reward, and pretreatment with TRPVI antagonists attenuated these effects. Microinjection of a selective TRPVI antagonist into the DSt significantly inhibited morphine-CPP. In addition, treatment with a TRPVI antagonist suppressed morphine-induced increases in mu-opioid receptor binding, adenylyl cyclase 1 (ACI), p38 mitogen-activated protein kinase (p38 MARK), and nuclear factor kappa B (NF-kappa B) expression in the DSt. Administering a p38 inhibitor not only prevented morphine-CPP, but also prevented morphine-induced NE-kappa B and TRPVI activation in the DSt. Furthermore, injecting an NF-kappa B inhibitor significantly blocked morphine-CPP. Our findings suggest that TRPVI in the DSt contribute to morphine reward via ACI, p38 MAPK, and NF-kappa B. Brain TRPVI may serve as a novel therapeutic target to treat morphine-addictive disorders.