A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”)

Thompson, M.R.; Callaghan, P.D.; Hunt, G.E.; Cornish, J.L.; McGregor, I.S.

doi:10.1016/j.neuroscience.2007.02.032

Cited by 237Neuroendocrine regulation and behaviorPsychedelics and Drug StudiesNeurotransmitter Receptor Influence on Behavior

A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”)

Thompson, M.R., Callaghan, P.D., Hunt, G.E., Cornish, J.L., McGregor, I.S.·2007·Neuroscience

DOI 10.1016/j.neuroscience.2007.02.032

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Abstract

The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT(1A) antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 microg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.

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The drug's empathogenic effects are given as a reason people use ecstasy recreationally and may add to its reinforcing properties.
“Such effects are cited as a motivation to use ecstasy recreationally [2–3] and may contribute to its reinforcing capacity [4].”
From Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others (2010) · cites this paper as [2]
MDMA increases rats' tendency to lie adjacent to one another, which is thought to indicate sociability.
“Notably, MDMA increases rats’ tendency to lie adjacent to each other, which is thought to indicate sociability (Morley et al. 2005; Thompson et al. 2007).”
From Effects of MDMA on sociability and neural response to social threat and social reward (2009) · cites this paper as Thompson et al. 2007
These rodent behavioral changes involve oxytocin release, and oxytocin receptor antagonism reduces MDMA's prosocial effects.
“These behavioral changes involve release of oxytocin (OT), a neuropeptide implicated in attachment and pair bonding, with OT receptor antagonism attenuating MDMA’s prosocial effects in rodents (Thompson et al. 2007).”
From Effects of MDMA on sociability and neural response to social threat and social reward (2009) · cites this paper as Thompson et al. 2007
In rats, moderate MDMA doses increase social interaction.
“In rats, moderate MDMA doses increase social interaction (Morley et al. 2005; Thompson et al. 2007).”
From Effects of MDMA on sociability and neural response to social threat and social reward (2009) · cites this paper as Thompson et al. 2007
OT is released by MDMA and is associated with the prosocial effects of this drug in humans and rats.
“With respect to drugs of abuse, OT is best known for being released by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy), and is associated with the prosocial effects of this drug in both humans and rats (Wolff et al 2006; Thompson et al 2007; Dumont et al 2009; Thompson et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Thompson et al 2007

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Self-citation

Authors: Thompson, M. R., Callaghan, P. D., Hunt, G. E., Cornish, J. L., & McGregor, I. S.
Affiliations: The University of Sydney (AU)
Macquarie University (AU)
Corresponding author: McGregor, I.S.
ORCID: Callaghan, P.D.
Hunt, G.E.
Cornish, J.L.
McGregor, I.S.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2007-05
Volume: 146
Issue: 2
Pages: 509-514
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2007.02.032
OpenAlex: W2109384015
Cited by: 237
References: 22
Citations by year: 2026: 4 · 2025: 7 · 2024: 12 · 2023: 11 · 2022: 8 · 2021: 12 · 2020: 11 · 2019: 16 · 2018: 13 · 2017: 12 · 2016: 18 · 2015: 18 · 2014: 16 · 2013: 23 · 2012: 9
FWCI: 15.10
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
Topics: Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: MDMA, ecstasy, oxytocin, 5-HT1A receptor, prosocial behavior, social interaction, supraoptic nucleus, paraventricular nucleus, WAY-100635, 8-OH-DPAT, drug reinforcement, affiliative behavior
MeSH terms: Animals, Behavior, Animal, Drug Interactions, Enzyme Inhibitors, Hallucinogens, Male, Oxytocin, Piperazines, Pyridines, Serotonin Antagonists, Social Behavior, Proto-Oncogene Proteins c-fos, Rats, Wistar, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, N-Methyl-3,4-methylenedioxyamphetamine, Receptor, Serotonin, 5-HT1A, Rats

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A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”)

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