Transient Receptor Potential Vanilloid Type 1 Channel May Modulate Opioid Reward

Transient receptor potential vanilloid type 1 (TRPV1), a nonselective cation channel, is a well-known pain-related receptor. TRPV1 involvement in morphine-induced antinociception, tolerance, and withdrawal symptoms has been previously reported. Emerging evidence indicates that TRPV1 may be related to both the cellular and behavioral effects of addictive drugs. In the present study, we investigated the role of TRPV1 in morphine reward using the conditioned place preference (CPP) paradigm in mice. Repeated morphine treatments upregulated TRPV1 expression in the dorsal striatum (DSt). Treatment with a TRPV1 agonist potentiated morphine reward, and pretreatment with TRPV1 antagonists attenuated these effects. Microinjection of a selective TRPV1 antagonist into the DSt significantly inhibited morphine-CPP. In addition, treatment with a TRPV1 antagonist suppressed morphine-induced increases in μ-opioid receptor binding, adenylyl cyclase 1 (AC1), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa B (NF-κB) expression in the DSt. Administering a p38 inhibitor not only prevented morphine-CPP, but also prevented morphine-induced NF-κB and TRPV1 activation in the DSt. Furthermore, injecting an NF-κB inhibitor significantly blocked morphine-CPP. Our findings suggest that TRPV1 in the DSt contribute to morphine reward via AC1, p38 MAPK, and NF-κB. Brain TRPV1 may serve as a novel therapeutic target to treat morphine-addictive disorders.