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MDMA-induced c-Fos expression in oxytocin-containing neurons is blocked by pretreatment with the 5-HT-1A receptor antagonist WAY 100635.
Brain Res Bull. 2011 Aug 10; 86(1-2):65-73.BR

Abstract

The popular party drug MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") increases sociability in both humans and laboratory animals. Recent research suggests that these prosocial effects may involve serotonin (5-HT)-stimulated hypothalamic release of the neuropeptide oxytocin. WAY 100635, a 5-HT(1A) receptor antagonist, prevents MDMA-induced increases in plasma oxytocin and also reduces MDMA-mediated increases in social interaction in rats. The present study used c-Fos immunohistochemistry to determine the possible role of 5-HT(1A) receptors in MDMA-mediated activation of oxytocin synthesizing neurons. Male Wistar rats (n=8/group) were administered MDMA (10 mg/kg, i.p.) with or without WAY 100635 (1 mg/kg, i.p.) pre-treatment and c-Fos expression was then assessed throughout the brain. MDMA significantly increased locomotor activity and this effect was partly prevented by WAY 100635, in agreement with previous studies. WAY 100635 significantly reduced MDMA-induced c-Fos expression in a subset of brain regions examined. A particularly prominent reduction was seen in the oxytocin-positive neurons of the supraoptic nucleus and paraventricular hypothalamus, with more modest reductions in the Islands of Calleja, median preoptic nucleus, somatosensory cortex and nucleus of the solitary tract. WAY 100635 did not alter MDMA-induced c-Fos expression in the striatum, thalamus, or central amygdala. These results indicate that MDMA's action on oxytocin producing cells in the hypothalamus is mediated through 5-HT(1A) receptors and that certain specific cortical, limbic and brainstem sites are also activated by MDMA via these receptors.

Authors+Show Affiliations

Discipline of Psychiatry, Sydney Medical School, University of Sydney, Concord Hospital, NSW, Australia. glenn.hunt@sydney.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21745546

Citation

Hunt, Glenn E., et al. "MDMA-induced c-Fos Expression in Oxytocin-containing Neurons Is Blocked By Pretreatment With the 5-HT-1A Receptor Antagonist WAY 100635." Brain Research Bulletin, vol. 86, no. 1-2, 2011, pp. 65-73.
Hunt GE, McGregor IS, Cornish JL, et al. MDMA-induced c-Fos expression in oxytocin-containing neurons is blocked by pretreatment with the 5-HT-1A receptor antagonist WAY 100635. Brain Res Bull. 2011;86(1-2):65-73.
Hunt, G. E., McGregor, I. S., Cornish, J. L., & Callaghan, P. D. (2011). MDMA-induced c-Fos expression in oxytocin-containing neurons is blocked by pretreatment with the 5-HT-1A receptor antagonist WAY 100635. Brain Research Bulletin, 86(1-2), 65-73. https://doi.org/10.1016/j.brainresbull.2011.06.011
Hunt GE, et al. MDMA-induced c-Fos Expression in Oxytocin-containing Neurons Is Blocked By Pretreatment With the 5-HT-1A Receptor Antagonist WAY 100635. Brain Res Bull. 2011 Aug 10;86(1-2):65-73. PubMed PMID: 21745546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MDMA-induced c-Fos expression in oxytocin-containing neurons is blocked by pretreatment with the 5-HT-1A receptor antagonist WAY 100635. AU - Hunt,Glenn E, AU - McGregor,Iain S, AU - Cornish,Jennifer L, AU - Callaghan,Paul D, Y1 - 2011/07/01/ PY - 2011/06/23/received PY - 2011/06/24/accepted PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2012/4/5/medline SP - 65 EP - 73 JF - Brain research bulletin JO - Brain Res. Bull. VL - 86 IS - 1-2 N2 - The popular party drug MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") increases sociability in both humans and laboratory animals. Recent research suggests that these prosocial effects may involve serotonin (5-HT)-stimulated hypothalamic release of the neuropeptide oxytocin. WAY 100635, a 5-HT(1A) receptor antagonist, prevents MDMA-induced increases in plasma oxytocin and also reduces MDMA-mediated increases in social interaction in rats. The present study used c-Fos immunohistochemistry to determine the possible role of 5-HT(1A) receptors in MDMA-mediated activation of oxytocin synthesizing neurons. Male Wistar rats (n=8/group) were administered MDMA (10 mg/kg, i.p.) with or without WAY 100635 (1 mg/kg, i.p.) pre-treatment and c-Fos expression was then assessed throughout the brain. MDMA significantly increased locomotor activity and this effect was partly prevented by WAY 100635, in agreement with previous studies. WAY 100635 significantly reduced MDMA-induced c-Fos expression in a subset of brain regions examined. A particularly prominent reduction was seen in the oxytocin-positive neurons of the supraoptic nucleus and paraventricular hypothalamus, with more modest reductions in the Islands of Calleja, median preoptic nucleus, somatosensory cortex and nucleus of the solitary tract. WAY 100635 did not alter MDMA-induced c-Fos expression in the striatum, thalamus, or central amygdala. These results indicate that MDMA's action on oxytocin producing cells in the hypothalamus is mediated through 5-HT(1A) receptors and that certain specific cortical, limbic and brainstem sites are also activated by MDMA via these receptors. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/21745546/MDMA_induced_c_Fos_expression_in_oxytocin_containing_neurons_is_blocked_by_pretreatment_with_the_5_HT_1A_receptor_antagonist_WAY_100635_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(11)00192-4 DB - PRIME DP - Unbound Medicine ER -