Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A.
Ema Alves, Teresa Summavielle, Cecília Juliana Alves, José Barata Antunes Custódio, Eduarda Fernandes, Maria de Lourdes Bastos, Maria Amélia Tavares, Félix Carvalho
Addiction Biology April 2009 DOI: 10.1111/j.1369-1600.2008.00143.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent rat model |
| Interventions | MDMA Clorgyline |
| Dose | 10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations |
| Measures | mitochondrial lipid peroxidation, protein carbonylation, expression of respiratory chain protein subunits NDII and COXI, serotonin-mediated behaviour, body temperature, mortality |
| Topics | MDMA |
| Key findings | In adolescent rats, MAO-A inhibition by clorgyline combined with a neurotoxic binge dose of MDMA produced synergistic serotonin-mediated behavioral and body-temperature effects and high mortality. Clorgyline did not protect against MDMA-induced mitochondrial lipid peroxidation, protein carbonylation, or reduced NDII and COXI expression, and it aggravated the COXI decrease. The authors conclude that concomitant use of MAO-A inhibitors and MDMA is contraindicated due to severe synergistic toxicity. |
Abstract
The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes British Journal of Pharmacology April 21, 2011
- Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics Experimental Neurology June 4, 2021
- PRECLINICAL STUDY: Acquisition and reinstatement of MDMA‐induced conditioned place preference in mice pre‐treated with MDMA or cocaine during adolescence Addiction Biology September 8, 2009
- Memory impairment and hippocampus specific protein oxidation induced by ethanol intake and 3, 4‐Methylenedioxymethamphetamine (MDMA) in mice Journal of Neurochemistry March 25, 2013
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Cites 9
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- Death following ingestion of MDMA (ecstasy) and moclobemide Addiction February 20, 2003
- Qualitative Review of Serotonin Syndrome, Ecstasy (MDMA) and the use of Other Serotonergic Substances: Hierarchy of Risk Australian & New Zealand Journal of Psychiatry July 25, 2007
- Effect of Repeated (‘Binge’) Dosing of MDMA to Rats Housed at Normal and High Temperature on Neurotoxicdamage to Cerebral 5-Ht and Dopamine Neurones Journal of Psychopharmacology September 1, 2004
and 4 more in the library