Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA.
Dmitry V Zaretsky, Maria V Zaretskaia, Joseph A Dimicco, Pamela J Durant, Christian T Ross, Daniel E. Rusyniak
Neuroscience Letters October 25, 2013 DOI: 10.1016/j.neulet.2013.07.053 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA WAY-100635 Muscimol aCSF |
| Dose | 7.5mg/kg i.v. |
| Topics | MDMA Serotonin |
| Keywords | 3,4-methylenedioxymethamphetamine 5-ht1a Acth Adrenocorticotropic hormone Hpa Pvh Paraventricular hypothalamus Serotonin 1a receptors Way-100635 Acsf Adrenocorticotropin releasing hormone Artificial cerebrospinal fluid Hypothalamic–pituitary–adrenal axis Serotonin-1a receptors |
| Key findings | Neurons in the paraventricular hypothalamus mediate ACTH responses to MDMA independently of serotonin-1a receptors, according to the authors. Systemic 5-HT1A blockade with WAY-100635 reduced ACTH after MDMA, but local PVH microinjection of WAY had no effect, whereas the inhibitory agonist muscimol significantly attenuated the ACTH rise (126 vs. 588 pg/ml, P<0.01). |
Abstract
Acute and chronic complications from the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) are linked to activation of the hypothalamic-pituitary-adrenal (HPA) axis. How MDMA activates the HPA axis is not known. HPA responses to stress are known to be mediated through the paraventricular (PVH) hypothalamus and to involve serotonin-1a (5-HT1A) receptors. We sought to determine if the PVH and 5-HT1A receptors were also involved in mediating HPA responses to MDMA. Rats were pretreated with either saline or a 5-HT1A antagonist, WAY-100635 (WAY), followed by a systemic dose of MDMA (7.5mg/kg i.v.). Animals pretreated with WAY had significantly lower plasma ACTH concentrations after MDMA. To determine if neurons in the PVH were involved, and if their involvement was mediated by 5-HT1A receptors, rats implanted with guide cannulas targeting the PVH were microinjected with the GABAA receptor agonist muscimol, aCSF, or WAY followed by MDMA. Compared to aCSF, microinjections of muscimol significantly attenuated the MDMA-induced rise in plasma ACTH (126 vs. 588pg/ml, P=<0.01). WAY had no effect. Our data demonstrates that neurons in the PVH, independent of 5-HT1A receptors, mediate ACTH responses to MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Acute Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate on Circulating Steroid Levels in Healthy Subjects Neuroendocrinology 2014
- The effect of MDMA on anterior pituitary hormones: a secondary analysis of a randomized placebo-controlled trial. Endocrine connections June 1, 2025
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
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