Abstract
The function of TRPV1 (transient receptor potential vanilloid subfamily, member 1) in the central nervous system is gradually elucidated. It has been recently proved to be expressed in nucleus accumbens (NAc), a region playing an essential role in mediating opioid craving and taking behaviors. Based on the general role of TRPV1 antagonist in blocking neural over-excitability by both pre- and post-synaptic mechanisms, TRPV1 antagonist capsazepine (CPZ) was tested for its ability to prohibit persistent opioid craving in rats. In the present study, we assessed the expression of TRPV1 in nucleus accumbens and investigated the effect of CPZ in bilateral nucleus accumbens on persistent morphine conditioned place preference (mCPP) in rats. We also evaluated the side-effect of CPZ on activity by comparing cross-beam times between groups. We found that morphine conditioned place preference increased the TRPV1 expression and CPZ attenuated morphine conditioned place preference in a dose-dependent and target–specific manner after both short- and long-term spontaneous withdrawal, reflected by the reduction of the increased time in morphine-paired side. CPZ (10 nM) could induce prolonged and stable inhibition of morphine conditioned place preference expression. More importantly, CPZ did not cause dysfunction of activity in the subjects tested, which indicates the inhibitory effect was not obtained at the sacrifice of regular movement. Collectively, these results indicated that injection of TRPV1 antagonist in nucleus accumbens is capable of attenuating persistent morphine conditioned place preference without affecting normal activity. Thus, TRPV1 antagonist is one of the promising therapeutic drugs for the treatment of opioid addiction.
Highlights
Opioid addiction is a type of complex brain disorder, which is characterized by uncontrollable opioid craving and compulsive opioid seeking and taking behavior regardless of consequences
Alcantara et al reported that morphine treatment increase the number of synapses of nucleus accumbens (NAc), which was due primarily to an increase in the number of asymmetric synapses, and Asymmetric synapses in the accumbens are characteristic of glutamatergic synapses formed by inputs from other area such as prefrontal cortex, hippocampus and so on [30]
We demonstrated that TRPV1 was increased in the nucleus accumbens of rats after morphine conditioned
Summary
Opioid addiction is a type of complex brain disorder, which is characterized by uncontrollable opioid craving and compulsive opioid seeking and taking behavior regardless of consequences. High incidence of drug craving and relapse to drug seeking and taking behaviors is the main obstacle for treatment [1]. There is still limited information about the function of central TRPV1 in drug addiction, especially in opioid addiction. It has been reported that TRPV1 antagonist decreased cocaineinduced cocaine-seeking behavior [10]. Both findings suggest the engagement of TRPV1 in drug addiction behaviors. Considering the limitation of the animal model used, the difference between opioid and psychostimulant dependence [11] 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
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