Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA

Dmitry Zaretsky, Maria V. Zaretskaia, Joseph A. DiMicco, Pamela J. Durant, Christian T. Ross, Daniel Rusyniak

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)42-46
Number of pages5
JournalNeuroscience Letters
Volume555
DOIs
StatePublished - Oct 25 2013

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N-Methyl-3,4-methylenedioxyamphetamine
Receptor, Serotonin, 5-HT1A
Adrenocorticotropic Hormone
Hypothalamus
Neurons
Muscimol
Serotonin 5-HT1 Receptor Antagonists
GABA-A Receptor Agonists
Microinjections
Amphetamine

Keywords

  • Adrenocorticotropic hormone
  • Amphetamine
  • MDMA
  • Paraventricular hypothalamus
  • Serotonin 1a receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA. / Zaretsky, Dmitry; Zaretskaia, Maria V.; DiMicco, Joseph A.; Durant, Pamela J.; Ross, Christian T.; Rusyniak, Daniel.

In: Neuroscience Letters, Vol. 555, 25.10.2013, p. 42-46.

Research output: Contribution to journalArticle

Zaretsky, Dmitry ; Zaretskaia, Maria V. ; DiMicco, Joseph A. ; Durant, Pamela J. ; Ross, Christian T. ; Rusyniak, Daniel. / Independent of 5-HT1A receptors, neurons in the paraventricular hypothalamus mediate ACTH responses from MDMA. In: Neuroscience Letters. 2013 ; Vol. 555. pp. 42-46.
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