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

doi:10.1016/j.pnpbp.2025.111260

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 and Biological Psychiatry March 20, 2025 DOI: 10.1016/j.pnpbp.2025.111260 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Experimental study Peer reviewed
Population	Rats
Interventions	subdiaphragmatic vagotomy MDMA
Dose	single oral dose
Topics	MDMA
Keywords	Gut-brain axis Oxytocin Paraventricular nucleus Supraoptic nucleus Vagus nerve Psychopharmacology Hormone regulation MDMA Research
Citations	4
Key findings	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.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study	Year	Design
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context)	1987	Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain	1987	Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells	2006	In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats	1998	Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA	1999	Observational cohort

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