3,4-Methylenedioxymethamphetamine (
MDMA)-induced neurotoxicity and the protective role of
monoamine oxidase-B (
MAO-B) inhibition were evaluated at the mitochondrial level in various regions of the adolescent rat brain. Four groups of adolescent male Wistar rats were used: (1) saline control, (2) exposed to
MDMA (4 x 10 mg/kg, i.p.; two hourly), (3) treated with
selegiline (2 mg/kg, i.
p.) 30 min before the same dosing of
MDMA, and (4) treated with
selegiline (2 mg/kg, i.p.). Body temperatures were monitored throughout the whole experiment. Animals were killed 2 weeks later, and mitochondria were isolated from several brain regions. Our results showed that "binge"
MDMA administration causes, along with sustained
hyperthermia, long-term alterations in brain mitochondria as evidenced by increased levels of
lipid peroxides and
protein carbonyls. Additionally, analysis of
mitochondrial DNA (
mtDNA) revealed that NDI
nicotinamide adenine dinucleotide phosphate dehydrogenase subunit I and NDII (
nicotinamide adenine dinucleotide phosphate dehydrogenase subunit II) subunits of mitochondrial complex I and
cytochrome c oxidase subunit I of complex IV suffered deletions in
MDMA-exposed animals. Inhibition of
MAO-B by
selegiline did not reduce
hyperthermia but reversed
MDMA-induced effects in the oxidative stress markers,
mtDNA, and related
protein expression. These results indicate that monoamine oxidation by
MAO-B with subsequent mitochondrial damage may be an important contributing factor for
MDMA-induced neurotoxicity.