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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neuropharmacology
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1507747
This article is part of the Research Topic Substance Use Disorder: Above and Beyond Addiction, Volume II View all 23 articles

Dezocine Modulates the Reinstatement of Conditioned Place Preference in Morphine-Dependent Rats via the Dopamine Reward Circuitry

Provisionally accepted
Yan He Yan He 1,2Zhi-Sheng Piao Zhi-Sheng Piao 3Yi Jia Yi Jia 3Hui-Qi Wu Hui-Qi Wu 3Xiaoqiang Wang Xiaoqiang Wang 4,5Weifeng Yu Weifeng Yu 4*Feixiang Wu Feixiang Wu 3*
  • 1 Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital affiliated to Naval Medical University, Shanghai, China
  • 2 Department of Anesthesiology, Fuzhou First Hospital, Fuzhou, Fujian Province, China
  • 3 Department of Critical Care Medicine, Eastern Hepatobiliary Surgery Hospital affiliated to Naval Medical University, Shanghai, China
  • 4 Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 5 Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China

The final, formatted version of the article will be published soon.

    Opioid addiction poses a significant public health challenge, with current therapies such as buprenorphine and methadone having limitations, including side effects and inadequate prevention of relapse. We constructed a morphine-induced conditioned place preference (CPP) model in rats to evaluate the effect of dezocine on addiction-related behaviors. Behavioral assessments were conducted for withdrawal symptoms and CPP reinstatement. To explore the mechanism, Western blot (WB) and immunofluorescence (IF) were employed to measure phosphorylated DARPP32 (p-DARPP32) and DOPA decarboxylase (DDC) expression in reward-related brain regions, including the nucleus accumbens (NAc), ventral tegmental area (VTA), hippocampus (HP), and prefrontal cortex (PFC). Dezocine effectively reduced withdrawal symptoms and prevented CPP reinstatement. Western blotting and immunofluorescence analysis demonstrated that dezocine significantly increased p-DARPP32 expression in the NAc, VTA, HP, and PFC, without altering DDC levels. These results suggest that dezocine's therapeutic effect may involve inhibiting kappa opioid receptor activation and enhancing dopamine signaling in reward-related brain circuitry. Our findings highlight dezocine as a promising candidate for opioid addiction treatment, providing new evidence for its clinical application in controlling withdrawal symptoms and preventing relapse.

    Keywords: Opioid-Related Disorders, Morphine Dependence, Dezocine, Therapeutics, Substance Withdrawal Syndrome

    Received: 08 Oct 2024; Accepted: 03 Feb 2025.

    Copyright: © 2025 He, Piao, Jia, Wu, Wang, Yu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Weifeng Yu, Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000, China
    Feixiang Wu, Department of Critical Care Medicine, Eastern Hepatobiliary Surgery Hospital affiliated to Naval Medical University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.