Blocking TRPV1 in nucleus accumbens inhibits persistent morphine conditioned place preference expression in rats
Authors: Jian Song
Peng Wang
Li-Jun Heng
Heng Guo
Guo-Dong Gao
Wei-Xin Yuan
Bo Huang
Guo-Zheng Xu
Lian-Ting Ma
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: TRPV1; central nervous system; nucleus accumbens; opioid craving; TRPV1 antagonist
Affiliations: 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., Department of Neurosurgery, Tangdu Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China., Department of Neurosurgery, PLA Chengdu General Hospital, Chengdu, Sichuan, China., Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei, China.

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. 

Retracted: Yes

PubPeer comments:
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 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0230396 After this article [1] was published, concerns were raised about results reported in Figs 2 and 3: There appear to be several vertical and horizontal discontinuities in both panels of Fig 2A. The 1w panel of Fig 3A appears similar to the 3w panel of Fig 3B, except for the dark circular features representative of immunogold labelling. In regard to Fig 2A, the authors provided raw image data and clarified that several bands had been rearranged in preparing the figure. The 1 mg kg, 3 mg kg, and 10 mg kg morphine data were obtained using different blots, the control data were mislabeled in the figure, and the control lane in the original figure applied only to the 1 mg kg samples. In addition, Fig 2A and 2B did not report data for saline-treated animals and as such were missing control findings needed to interpret the results. For Fig 3, the authors provided a replacement image for the 3w panel of Fig 3B along with raw image data to support Fig 3A and the 1d, 1w panels of Fig 3B. They noted that the other electron microscopy data are no longer available, and they were unable to clarify the concern about the original figure. In light of the unresolved concerns about Fig 3 and questions around the controls for the experiments reported in Fig 2, the PLOS ONE Editors retract this article. G-DG notified the journal that all authors agree to retraction. The other authors either did not respond directly or could not be reached. Reference 1.Heng L-J, Huang B, Guo H, Ma L-T, Yuan W-X, Song J, et al. (2014) Blocking TRPV1 in Nucleus Accumbens Inhibits Persistent Morphine Conditioned Place Preference Expression in Rats. PLoS ONE 9(8): e104546. https: doi.org 10.1371 journal.pone.0104546 ,