Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats

Thompson, Murray R.; Callaghan, Paul D.; Hunt, Glenn E.; McGregor, Iain S.

doi:10.1016/j.pnpbp.2008.01.014

Cited by 25Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorNeuroendocrine regulation and behavior

Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats

Thompson, Murray R., Callaghan, Paul D., Hunt, Glenn E., McGregor, Iain S.·2008·Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI 10.1016/j.pnpbp.2008.01.014

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Abstract

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

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Since everyone had used ecstasy or MDMA before, the results might not apply to people with no prior exposure.
“A final limitation is that, for ethical reasons, all participants had prior experience with ecstasy or MDMA, so the findings may not generalize to MDMA-naive individuals [see 42].”
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 [42]

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Authors: Thompson, M. R., Callaghan, P. D., Hunt, G. E., & McGregor, I. S.
Affiliations: The University of Sydney (AU)
Corresponding author: McGregor, Iain S.
ORCID: Callaghan, Paul D.
Hunt, Glenn E.
McGregor, Iain S.
Venue: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher: Elsevier BV
Published: 2008-05
Volume: 32
Issue: 4
Pages: 1013-1021
ISSN: 0278-5846 (ISSN-L)
DOI: 10.1016/j.pnpbp.2008.01.014
OpenAlex: W2005645528
Cited by: 25
References: 64
Citations by year: 2026: 1 · 2025: 1 · 2021: 2 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3
FWCI: 3.35
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
Funders: National Health and Medical Research Council
National Medical Research Council
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords: MDMA, ecstasy, social interaction, prosocial behavior, drug tolerance, 5-HT1A receptor, 8-OH-DPAT, serotonin depletion, 5-hydroxyindoleacetic acid, prefrontal cortex, neural adaptation, social dysfunction
MeSH terms: Animals, Body Temperature, Brain Chemistry, Chromatography, High Pressure Liquid, Male, Piperazines, Pyridines, Serotonin Antagonists, Social Behavior, Rats, Wistar, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Adrenergic Uptake Inhibitors, N-Methyl-3,4-methylenedioxyamphetamine, Receptor, Serotonin, 5-HT1A, Rats

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Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats

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