Serotonergic-dopaminergic mediation of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
Pharmacology, Biochemistry, and Behavior December 1988 DOI: 10.1016/0091-3057(88)90390-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal behavioral pharmacology experiments Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA MDE norfenfluramine TFMPP pirenperone CGS 10746B haloperidol |
| Dose | 1.5 mg/kg (+/-)-MDMA |
| Topics | MDMA Serotonin |
| Key findings | The authors conclude that MDMA's discriminative stimulus effects are solely serotonergic at 20 minutes postadministration, but at 105 minutes a weak dopaminergic component emerges alongside the predominant serotonergic effect. They propose this biphasic serotonergic-then-dopaminergic action may explain reported human experiences with MDMA and inconsistent results in the literature. |
Abstract
A series of three experiments were conducted to investigate the possible serotonergic and dopaminergic mediation of the discriminative stimulus properties of the "designer" drug MDMA. In Experiment 1, rats trained to discriminate 1.5 mg/kg (+/-)-MDMA from its vehicle at 20 min postadministration were shown to generalize to another drug of abuse, N-ethyl-3,4-methylenedioxyamphetamine (MDE) and to the serotonergically-active agents norfenfluramine and TFMPP. In contrast, testing of various dopaminergically-active agonists did not result in MDMA-like responding. In Experiment 2, dopaminergic and serotonergic antagonist were employed to observe their effect upon MDMA discrimination at 20 min postinjection. The serotonin antagonist pirenperone significantly decreased MDMA discrimination, whereas the dopamine decreasing drugs CGS 10746B and haloperidol had no effect. In Experiment 3, another group of rats were trained to discriminate MDMA at 105 min postadministration to investigate if, at this (later) time, the dopaminergic properties of MDMA may be more salient. Indeed, the dopaminergically-active drugs had a heightened effect upon MDMA at this later time, although the serotonergic component of the MDMA discriminative stimulus was predominant. The results suggest that the effects of MDMA at 20 min postadministration are solely serotonergic in nature. At 105 min postinjection there appears to be the presence of a weak dopaminergic component. This biphasic serotonergic-then-dopaminergic action of MDMA may explain the reported human experience with the drug, as well as the often controversial results in the literature.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 48
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
- NBOMes–Highly Potent and Toxic Alternatives of LSD Frontiers in Neuroscience February 26, 2020
and 43 more in the library
Cites 7
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- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- Mescaline elicits behavioral effects in cats by an action at both serotonin and dopamine receptors European Journal of Pharmacology December 1, 1983
- Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE"). Pharmacology, Biochemistry, and Behavior October 1987
and 2 more in the library