Direct central effects of acute methylenedioxymethamphetamine on serotonergic neurons.
European Journal of Pharmacology October 26, 1988 DOI: 10.1016/0014-2999(88)90154-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (preclinical study in rats) Peer reviewed |
|---|---|
| Population | Rats (with in vitro comparisons using cortical slices and the mouse mastocytoma cell line P-815) |
| Topics | MDMA Serotonin |
| Key findings | Acute peripheral MDMA, either stereoisomer, rapidly lowered tryptophan hydroxylase activity in several rat brain regions before serotonin concentrations fell, with an early rise in 5-hydroxyindole acetic acid suggesting increased serotonin turnover. The effect was not reproduced in cortical slices or the P-815 cell line and did not follow direct regional injection, but did occur when brain MDMA levels were held steady by constant intracerebroventricular infusion. The authors conclude the effect on serotonin synthesis is a direct central action of the drug, possibly triggered by sustained increases in transmitter turnover. |
Abstract
Acute peripheral administration of either the (+) or (-) stereoisomer of methylenedioxymethamphetamine (MDMA) to rats results in a rapid loss of tryptophan hydroxylase (TPH) activity in several brain regions. This decline in enzyme activity precedes a decrease in serotonin (5-HT) concentrations in the same areas. An initial rise in the concentration of 5-hydroxyindole acetic acid after drug administration suggests that an increase in the turnover of 5-HT is an early event in the development of these changes. Unsuccessful attempts to reproduce the in vivo effects of MDMA on TPH activity using in vitro preparations such as cortical slices or the mouse mastocytoma cell line, P-815, suggested a requirement for an intact neuronal system or metabolism of the drug. Injection of MDMA directly into several brain regions also had no effect on TPH activity or 5-HT concentrations. However, when brain concentrations of MDMA were maintained using a constant i.c.v. infusion, TPH activity declined as observed following peripheral administration. The results, therefore, indicate that the acute effect of MDMA on 5-HT synthesis is a direct central effect of the drug which may be triggered by a sustained increase in transmitter turnover.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 36
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Glutathione and N-Acetylcysteine Conjugates of α-Methyldopamine Produce Serotonergic Neurotoxicity: Possible Role in Methylenedioxyamphetamine-Mediated Neurotoxicity Chemical Research in Toxicology November 19, 1999
- Effects of Intracerebroventricular Administration of 5-(Glutathion-S-yl)-α-methyldopamine on Brain Dopamine, Serotonin, and Norepinephrine Concentrations in Male Sprague-Dawley Rats Chemical Research in Toxicology 1996
- Mechanism of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy)‐mediated mitochondrial dysfunction in rat liver PROTEOMICS September 1, 2008
- Serotonergic Neurotoxicity of 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylendioxymethamphetamine (Ecstasy) Is Potentiated by Inhibition of γ-Glutamyl Transpeptidase Chemical Research in Toxicology May 31, 2001
and 31 more in the library
Cites 9
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Hallucinogenic Amphetamine Selectively Destroys Brain Serotonin Nerve Terminals Science September 6, 1985
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- Acute administration of methylenedioxymethamphetamine: comparison with the neurochemical effects of its N-desmethyl and N-ethyl analogs. European Journal of Pharmacology April 7, 1987
and 4 more in the library