The effects of methylenedioxymethamphetamine (MDMA, "Ecstasy") on monoaminergic neurotransmission in the central nervous system.
S R White, T Obradovic, K M Imel, M J Wheaton
Progress in Neurobiology August 1996 DOI: 10.1016/0301-0082(96)00027-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Awake, behaving laboratory animals |
| Topics | MDMA |
| Key findings | Single MDMA doses increase extracellular dopamine and serotonin in the nucleus accumbens and other reward-related brain regions in laboratory animals, and most reported behavioral and electrophysiological effects appear mediated by these increases. Repeated or high-dose MDMA is neurotoxic to a subpopulation of forebrain-projecting serotonin axons and is associated with long-lasting changes in dopamine and serotonin neurotransmission. Whether such changes relate to depression reported by some frequent users remains to be determined. |
Abstract
Methylenedioxymethamphetamine (MDMA, Ecstasy) is a popular recreationally used drug among young people in Europe and North America. The recent surge in use of MDMA and increasing concerns about possible toxic effects of the drug have inspired a great deal of research into the mechanisms by which the drug may affect the central nervous system. This paper reviews studies on the neurochemical, behavioral and neurophysiological effects of MDMA, with emphasis on MDMA effects in regions of the brain that have been implicated in reward. Experiments in awake, behaving laboratory animals have demonstrated that single injections of MDMA increase extracellular levels of the neurotransmitters dopamine (DA) and serotonin (5HT) in the nucleus accumbens and in several other brain regions that are important for reward. Most of the behavioral and electrophysiological changes that have been reported to date for single doses of MDMA appear to be mediated by this MDMA-induced increase in extracellular DA and 5HT. As an example, MDMA-induced hyperthermia and locomotor hyperactivity in laboratory animals can be blocked by administering drugs that prevent MDMA-induced 5HT release and can be attenuated by administering 5HT receptor antagonists, whereas effects of MDMA on delayed reinforcement tasks appear to be mediated by MDMA-induced increases in extracellular DA. Similarly, the effects of MDMA on neuronal excitability in the nucleus accumbens and in several other brain regions can be prevented by administering drugs that block MDMA-induced 5HT release and can be attenuated by depleting brain DA levels or by administering either DA D1 receptor antagonists or 5HT receptor antagonists. In addition to the acute effects of MDMA, it is now well established that repeated or high-dose administration of MDMA is neurotoxic to a subpopulation of 5HT-containing axons that project to the forebrain in laboratory animals. Recent studies have shown that this neurotoxic effect of MDMA is associated with long-duration changes in both DA and 5HT neurotransmission in the nucleus accumbens. Whether these long-duration changes in neurotransmission might be related to reports of depression and other psychopathologies by some frequent users of MDMA remains to be determined. Methylene-dioxymethamphetamine has been found to increase extracellular levels of norepinephrine and to alter brain levels of several neuropeptides as well as altering levels of DA and 5HT. Much additional research is required to understand the multiple ways in which this complex drug may alter neurotransmission in the brain, both acutely and in the long term.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 65
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
- The content of ecstasy tablets: implications for the study of their long‐term effects Addiction December 1, 2002
- The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3, 4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers Journal of Psychopharmacology May 1, 2000
- A study of the mechanisms involved in the neurotoxic action of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain British Journal of Pharmacology December 1, 2001
and 60 more in the library
Cites 49
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
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