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Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A.
Addict Biol. 2009 Apr; 14(2):185-93.AB

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.

Authors+Show Affiliations

Grupo Neurocomportamento, Instituto de Biologia Molecular e Celular (IBMC), University of Porto (UP), Porto, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19076925

Citation

Alves, Ema, et al. "Ecstasy-induced Oxidative Stress to Adolescent Rat Brain Mitochondria in Vivo: Influence of Monoamine Oxidase Type A." Addiction Biology, vol. 14, no. 2, 2009, pp. 185-93.
Alves E, Summavielle T, Alves CJ, et al. Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. Addict Biol. 2009;14(2):185-93.
Alves, E., Summavielle, T., Alves, C. J., Custódio, J. B., Fernandes, E., de Lourdes Bastos, M., Tavares, M. A., & Carvalho, F. (2009). Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. Addiction Biology, 14(2), 185-93. https://doi.org/10.1111/j.1369-1600.2008.00143.x
Alves E, et al. Ecstasy-induced Oxidative Stress to Adolescent Rat Brain Mitochondria in Vivo: Influence of Monoamine Oxidase Type A. Addict Biol. 2009;14(2):185-93. PubMed PMID: 19076925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. AU - Alves,Ema, AU - Summavielle,Teresa, AU - Alves,Cecília Juliana, AU - Custódio,José Barata Antunes, AU - Fernandes,Eduarda, AU - de Lourdes Bastos,Maria, AU - Tavares,Maria Amélia, AU - Carvalho,Félix, Y1 - 2008/12/12/ PY - 2008/12/17/entrez PY - 2008/12/17/pubmed PY - 2009/8/6/medline SP - 185 EP - 93 JF - Addiction biology JO - Addict Biol VL - 14 IS - 2 N2 - 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. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/19076925/Ecstasy_induced_oxidative_stress_to_adolescent_rat_brain_mitochondria_in_vivo:_influence_of_monoamine_oxidase_type_A_ L2 - https://doi.org/10.1111/j.1369-1600.2008.00143.x DB - PRIME DP - Unbound Medicine ER -