Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference
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...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59859-z |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ying-jie Cheng |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-e617dd210bf84f3480d30c71577594ff |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
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| spelling | doaj-art-e617dd210bf84f3480d30c71577594ff2025-08-20T03:48:15ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59859-zOxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preferenceYing-jie Cheng0Gui-ying Zan1Ying-zhi Deng2Di Deng3Man-qing Wu4Jing-rui Chai5Yu-jun Wang6Jing-gen Liu7Min Zhao8Shanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesShanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineAbstract 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).https://doi.org/10.1038/s41467-025-59859-z |
| spellingShingle | 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 Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference Nature Communications |
| title | Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference |
| title_full | Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference |
| title_fullStr | Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference |
| title_full_unstemmed | Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference |
| title_short | Oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine-conditioned place preference |
| title_sort | oxytocinergic input from the paraventricular nucleus to the nucleus accumbens core modulates methamphetamine conditioned place preference |
| url | https://doi.org/10.1038/s41467-025-59859-z |
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