title: Blocking TRPV1 in nucleus accumbens inhibits persistent morphine conditioned place preference expression in rats.
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.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Heng
authors.affiliation: Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, PLA Chengdu General Hospital, Chengdu, Sichuan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.
authors.forename: Lian-Ting
authors.initials: LT
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.
authors.forename: Guo-Zheng
authors.initials: GZ
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D066249:Craving / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D016253:Microscopy, Immunoelectron; D009020:Morphine; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D009020:Morphine; C071423:capsazepine; D002211:Capsaicin