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.