MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum
H. S. Fischer, Gerald Zernig, Dieter S. Schatz, Christian Humpel, Alois Saria
European Journal of Neuroscience April 1, 2000 DOI: 10.1046/j.1460-9568.2000.00004.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat striatal slices |
| Intervention | MDMA |
| Dose | 10–300 μM |
| Topics | MDMA Serotonin |
| Keywords | Dopamine Muscarinic acetylcholine receptor Pharmacology Neurotransmitter Histamine Striatum Neurochemical Cholinergic 5-HT Receptor Endocrinology |
| Citations | 54 |
| Key findings | MDMA increases acetylcholine release in rat striatal slices via activation of histamine H1 receptors, independent of dopamine, serotonin, or glutamate receptor pathways. |
Abstract
Abstract The pharmacological basis of acute (±)‐MDMA (3,4‐methylenedioxymethamphetamine) intoxication still awaits full characterization. According to present knowledge, MDMA enhances the release of serotonin and dopamine in striatal slices and interacts with different types of receptors such as 5‐HT 2 (5‐hydroxytryptamine or serotonin), M 1 and M 2 muscarinic acetylcholine (ACh), and histamine H 1 receptors. Currently, no information is available about the influence of (±)‐MDMA on striatal cholinergic neurotransmission. In the present study, we used the in vitro perfusion technique to investigate the effect of (±)‐MDMA on ACh release in rat striatal slices. Perfusions with (±)‐MDMA (10–300 μ m ) resulted in a dose‐dependent increase of spontaneous ACh release (EC 50 ≈ 30 μ m ). The effect was reversible and Ca ++ ‐ and tetrodotoxin‐sensitive. To determine the neurochemical pathways underlying this response, we perfused with (±)‐MDMA in the presence of various inhibitors of neurotransmitter receptors. Blockade of glutamate or muscarinic ACh receptors as well as 5‐HT 1 , 5‐HT 2 , 5‐HT 3C or dopamine D 2 receptors did not modulate (±)‐MDMA–induced ACh release. However, the presence of histamine H 1 receptor antagonists in the perfusion medium abolished (±)‐MDMA‐induced ACh release. The present data clearly demonstrate that (±)‐MDMA enhances the activity of striatal cholinergic neurons and suggest an involvement of histamine H 1 receptors. The effect is not mediated by glutamate and does not involve the activation of receptors of dopamine D 2 , 5‐HT 1 , 5‐HT 2 , 5‐HT 3C or muscarinic ACh. Considering the relatively high affinity of (±)‐MDMA for the H 1 histamine receptor (Ki 6 μ m ), a direct activation of this type of receptor might represent a plausible mechanism for (±)‐MDMA‐induced ACh release.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 17
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- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- The effects of MDMA on socio-emotional processing: Does MDMA differ from other stimulants? Journal of Psychopharmacology August 26, 2016
- Acute Psychological and Neurophysiological Effects of MDMA in Humans Journal of Psychoactive Drugs June 1, 2002
- In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys. Experimental and Clinical Psychopharmacology February 1, 2008
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Cites 6
- 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
- Potentiation of 3,4-methylenedioxymethamphetamine-induced dopamine release and serotonin neurotoxicity by 5-HT2 receptor agonists. European Journal of Pharmacology November 3, 1994
- Blockade of Striatal 5‐Hydroxytryptmine2Receptors Reduces the Increase in Extracellullar Concentrations of Dopamine Produced by the Amphhetamine analogue 3,4‐Methylenedioxymethamphetamine Journal of Neurochemistry April 1, 1994
- Modulation of methylenedioxymethamphetamine-induced striatal dopamine release by the interaction between serotonin and gamma-aminobutyric acid in the substantia nigra. Journal of Pharmacology and Experimental Therapeutics June 1, 1995
- Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). Psychopharmacology June 1995
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