Subdiaphragmatic vagotomy reduces hypothalamic oxytocin expression and blood levels after oral MDMA administration in male rats.
Yong Yue, Xiayun Wan, Guilin Liu, Tingting Zhu, Dan Xu, Mingming Zhao, Yi Cai, Rumi Murayama, Hirofumi Hashimoto, Naohiko Anzai, Kenji Hashimoto
Progress in neuro-psychopharmacology & biological psychiatry March 20, 2025 DOI: 10.1016/j.pnpbp.2025.111260 via PubMed
Summary
AI-generated from the abstractThe gut-brain axis, specifically the subdiaphragmatic vagus nerve, is critical for MDMA's effects on the oxytocin system in rats. Cutting this nerve (subdiaphragmatic vagotomy) lowered baseline oxytocin levels in the blood and reduced oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus. It also dampened MDMA-induced increases in blood oxytocin and the expression of oxytocin and c-Fos in those brain regions. The findings suggest the vagus nerve mediates brain-body communication that underlies MDMA's pharmacological actions on oxytocin.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | subdiaphragmatic vagotomy MDMA |
| Dose | single oral dose |
| Keywords | Gut-brain axis Oxytocin Paraventricular nucleus Supraoptic nucleus Vagus nerve |
| Citations | 4 |
| Key finding | Subdiaphragmatic vagotomy reduced baseline and MDMA-induced plasma oxytocin levels and hypothalamic oxytocin and c-Fos expression, indicating the vagus nerve mediates MDMA's effects on the oxytocin system. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is a widely recognized entactogen frequently used recreationally. It is known for its interaction with the serotonin and oxytocin systems, which underlie its entactogenic effects in humans. Recently, we demonstrated that the gut-brain axis, mediated by the subdiaphragmatic vagus nerve, contributes to MDMA-induced resilience enhancement in rodents. This study investigates whether subdiaphragmatic vagotomy (SDV) affects plasma oxytocin levels and the expression of oxytocin and c-Fos in the hypothalamus following a single oral dose of MDMA in rats. SDV significantly reduced baseline plasma oxytocin levels and oxytocin expression in the paraventricular and supraoptic nuclei of the hypothalamus. Furthermore, SDV markedly attenuated MDMA-induced increases in plasma oxytocin and the expression of oxytocin and c-Fos in these hypothalamic regions. These findings suggest that the subdiaphragmatic vagus nerve plays a critical role in brain-body communication, mediating MDMA's pharmacological effects on the oxytocin system.