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Examining the role of oxytocin in the interoceptive effects of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) using a drug discrimination paradigm in the rat

Jillian H. Broadbear, Brendan J. Tunstall, Katherine Beringer

Addiction Biology November 11, 2010 DOI: 10.1111/j.1369-1600.2010.00267.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Drug discrimination paradigm Peer reviewed
Sample size 24
Population Male and female Sprague Dawley rats
Interventions carbetocin atosiban imipramine
Topics MDMA Serotonin
Keywords Oxytocin receptor Amphetamine Hallucinogen Pharmacology 5-HT Receptor Agonist Antidepressant Stimulant
Citations 38
Key points Oxytocin receptor activation is a key MDMA-specific interoceptive cue that distinguishes it from amphetamine in rats.

Abstract

ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) use results in distinctive mood changes of a prosocial nature, most likely through its enhancement of serotonin (5HT) neurotransmission. Activation of 5HT‐1A postsynaptic receptors has been shown to stimulate the release of oxytocin in the central nervous system where it regulates aspects of mood and behavior. Using a drug discrimination paradigm, we examined whether modulation of oxytocin receptor activity would affect conditioned behavioral responses to MDMA. Male and female Sprague Dawley rats ( n = 24) were trained to reliably differentiate between MDMA and a related stimulant, amphetamine (AMP), and saline using a three‐lever drug discrimination paradigm. The extent to which substitution with carbetocin (an oxytocin analog) or co‐administration with atosiban (an oxytocin receptor antagonist) affected drug‐appropriate responding was evaluated. The tricyclic antidepressant imipramine was included as a negative control. The results supported the hypotheses that substitution with an oxytocin analog (carbetocin) would partially generalize to the MDMA training cue, whereas blocking oxytocin receptors with atosiban would result in a selective disruption of MDMA––but not AMP‐appropriate responding. These findings were specific to the oxytocin receptor ligands as imipramine pre‐treatment did not affect drug‐appropriate responding. The results of this study implicate oxytocin receptor activation as a key MDMA‐specific interoceptive cue in male and female rats and support the conclusion that this is one of the features of MDMA's subjective effects that distinguishes it from AMP.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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MDMA Serotonin