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Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference

Author

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  • Ying-jie Cheng

    (Shanghai Jiao Tong University School of Medicine)

  • Gui-ying Zan

    (Chinese Academy of Sciences)

  • Ying-zhi Deng

    (Shanghai Jiao Tong University School of Medicine)

  • Di Deng

    (Shanghai Jiao Tong University School of Medicine)

  • Man-qing Wu

    (Shanghai Jiao Tong University School of Medicine)

  • Jing-rui Chai

    (Chinese Academy of Sciences)

  • Yu-jun Wang

    (Chinese Academy of Sciences)

  • Jing-gen Liu

    (Chinese Academy of Sciences
    Key Laboratory of Acupuncture and Neurobiology of Zhejiang Province)

  • Min Zhao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Key Laboratory of Psychotic Disorders)

Abstract

Methamphetamine (METH) is a highly addictive psychostimulant, yet its addiction mechanisms remain unclear. Oxytocin (OXT), a neuropeptide, shows promise in reducing METH addiction, but how OXT exerts its effects is poorly understood. Using conditioned place preference (CPP), we first found that intranasal OXT other than Arginine Vasopressin (AVP) administration suppressed METH-CPP in mice, which could be reversed by OXT receptors (OXTRs) blockade in the nucleus accumbens (NAc) core. Activating OXTRs in the NAc core similarly reduced METH-CPP. Then, we found repeated METH exposure inhibited oxytocinergic neurons within the paraventricular nucleus (PVN) and lowered PVN OXT protein level. Chemogenetic activation of PVN oxytocinergic neurons (PVNOXT) blocked METH-CPP. Furthermore, METH inhibited PVNOXT-NAc core circuit other than PVNOXT-NAc shell circuit. Activation of PVNOXT-NAc core circuit significantly inhibited METH-CPP. This study reveals METH may impair the endogenous OXT system, especially the PVNOXT-NAc core circuit, highlighting OXT’s therapeutic potential for METH use disorder (MUD).

Suggested Citation

  • Ying-jie Cheng & Gui-ying Zan & Ying-zhi Deng & Di Deng & Man-qing Wu & Jing-rui Chai & Yu-jun Wang & Jing-gen Liu & Min Zhao, 2025. "Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59859-z
    DOI: 10.1038/s41467-025-59859-z
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    References listed on IDEAS

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    1. Gül Dölen & Ayeh Darvishzadeh & Kee Wui Huang & Robert C. Malenka, 2013. "Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin," Nature, Nature, vol. 501(7466), pages 179-184, September.
    2. Romain Nardou & Eastman M. Lewis & Rebecca Rothhaas & Ran Xu & Aimei Yang & Edward Boyden & Gül Dölen, 2019. "Oxytocin-dependent reopening of a social reward learning critical period with MDMA," Nature, Nature, vol. 569(7754), pages 116-120, May.
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