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

作者：Ying-Jie Cheng, Gui‐Ying Zan, Ying-Zhi Deng, Di Deng, Manqing Wu, Jing‐Rui Chai, Yujun Wang, Jing‐Gen Liu, Min Zhao · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-59859-z · 被引用次数：4 · 研究领域：Neuroendocrine regulation and behavior、Infant Health and Development、Attachment and Relationship Dynamics

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). The mechanisms whereby METH yields strong addiction potential is not fully understood. Here, authors show that METH may impair the function of the endogenous OXT system, particularly the PVNOXT-NAc core pathway, suggesting OXT-based therapies for METH use disorder (MUD).