Previous research suggested that repeated systematic blockade of TRPV1 by capsazepine, a TRPV1 antagonist, significantly reduced naloxone-induced withdrawal symptoms. However, there was no further tests of the effect of CPZ on morphine craving or relapse, which is the core process of addiction. Recently, it has been reported that TRPV1 antagonist decreased cocaineinduced cocaine-seeking behavior. Both findings suggest the engagement of TRPV1 in drug addiction behaviors. However, considering the limitation of the animal model used, the difference between opioid and psychostimulant dependence and the peripheral effects accompanying systematic delivery of TRPV1 blocker, further studies are needed to clarify the central action site and behavioral role for TRPV1 in opioid relapse. Nucleus accumbens was known as a critical region in mediating opioid relapse, and has been found to express TRPV1. Anatomical and electrophysiological studies suggest the possible subcellular localization of NAc TRPV1 is mainly in the presynaptic terminals and the cell bodies. Presynaptic TRPV1 has been proved to facilitate glutamate release and accordingly potentiate glutamatergic transmission in widespread brain areas. Masitinib Importantly, the enhancement of glutamatergic synaptic strength via increased presynaptic release in NAc is an essential neuroadaptation during withdrawal associated with opioid dependence. Blockade or attenuation of NAc glutamatergic transmission to reduce the excitatory drive may prevent relapse to opioid use. In another aspect, TRPV1 present in the cell bodies are proposed to modulate neuronal activity. TRPV1 agonist could increase the spike frequency of neurons in ventral tegmental area. These observations strongly suggested that NAc TRPV1 antagonism might perform anti-relapse effect by limiting neuronal activity and diminishing the efficacy of excitatory inputs from presynaptic terminals, which could reduce morphine conditioned place preference expression. Taken together, the TRPV1 receptor in nucleus accumbens could be a potential target for preventing opioid relapse. In the present study, we test the effect of blocking TRPV1 in NAc on persistent mCPP expression in rats and assess the influence of TRPV1 antagonist on motor activity in the same subjects. Alcantara et al. reported that morphine treatment increase the number of synapses of NAc, which was due primarily to an increase in the number of asymmetric synapses, and Asymmetric synapses in the accumbens are characteristic of glutamaterging.