Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice.
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
Neurotoxicity Research April 2018 DOI: 10.1007/s12640-017-9831-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | MDMA Caffeine |
| Duration | Chronic administration (duration not specified) |
| Measures | in vivo microdialysis, HPLC with electrochemical detection, alkaline comet assay, immunohistochemistry, quantitative PCR, open-field (OF) test, novel object recognition (NOR) test |
| Topics | MDMA Serotonin |
| Keywords | Caffeine Dopamine Mice Microdialysis Oxidative stress |
| Key findings | Caffeine potentiated MDMA-induced dopamine release while inhibiting serotonin release in the mouse striatum, and exacerbated MDMA-induced oxidative DNA damage. It diminished the MDMA-induced decrease in striatal dopamine transporter density but worsened the decrease in serotonin transporter density in the frontal cortex. Caffeine did not affect MDMA-induced changes in striatal prodynorphin expression or exploratory and locomotor activity, though novel object exploration was reduced by both drugs. |
Abstract
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration. To find out whether caffeine aggravates MDMA neurotoxicity, the content of DA and 5-HT, density of brain DAT and SERT, and oxidative damage of nuclear DNA were determined. Furthermore, the effect of caffeine on MDMA-induced changes in striatal dynorphin and enkephalin and on behavior was assessed. The DA and 5-HT release was determined with in vivo microdialysis, and the monoamine contents were measured by HPLC with electrochemical detection. DNA damage was assayed with the alkaline comet assay. DAT and SERT densities were determined by immunohistochemistry, while prodynorphin (PDYN) and proenkephalin were determined by quantitative PCR reactions. The behavioral changes were measured by the open-field (OF) test and novel object recognition (NOR) test. Caffeine potentiated MDMA-induced DA release while inhibiting 5-HT release in the mouse striatum. Caffeine also exacerbated the oxidative damage of nuclear DNA induced by MDMA but diminished DAT decrease in the striatum and worsened a decrease in SERT density produced by MDMA in the frontal cortex. Neither the striatal PDYN expression, increased by MDMA, nor exploratory and locomotor activities of mice, decreased by MDMA, were affected by caffeine. The exploration of novel object in the NOR test was diminished by MDMA and caffeine. Our data provide evidence that long-term caffeine administration has a powerful influence on functions of dopaminergic and serotonergic neurons in the mouse brain and on neurotoxic effects evoked by MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 16
- 3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & Behavior February 1, 2019
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- MDMA/ecstasy use and psilocybin use are associated with lowered odds of psychological distress and suicidal thoughts in a sample of US adults Journal of Psychopharmacology 2022
- Lifetime use of MDMA/ecstasy and psilocybin is associated with reduced odds of major depressive episodes Journal of Psychopharmacology 2022
- Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats Neurotoxicity Research December 18, 2020
and 11 more in the library
Cites 24
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 2000
- 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
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- 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
- MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding European Journal of Neuroscience November 16, 2007
and 19 more in the library