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Updated: Jul 11, 2026
A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria
Ema Alves1, Teresa Summavielle, Cecília Juliana Alves
1Neurobehaviour Unit, Instituto de Biologia Molecular e Celular, Medical School of Porto, University of Porto, 4099-002 Porto, Portugal.
Abstract:
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.
Insights
Monoamine oxidase-B (MAO-B) inhibition protected against 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity by reducing mitochondrial damage and oxidative stress in adolescent rats. Selegiline treatment reversed MDMA-induced alterations in brain mitochondria.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA) is known to cause neurotoxicity.
- Mitochondrial dysfunction is implicated in MDMA-induced neurotoxicity.
- The role of monoamine oxidase-B (MAO-B) in this process requires further investigation.
Purpose of the Study:
- To investigate the effects of MDMA on brain mitochondria in adolescent rats.
- To evaluate the protective role of MAO-B inhibition against MDMA-induced mitochondrial neurotoxicity.
Main Methods:
- Adolescent male Wistar rats were administered MDMA or saline.
- Some groups received selegiline, an MAO-B inhibitor, before MDMA exposure.
- Mitochondria were isolated from brain regions 2 weeks post-treatment for biochemical analysis, including lipid peroxides, protein carbonyls, and mitochondrial DNA (mtDNA) deletions.
Main Results:
- MDMA administration led to sustained hyperthermia, increased oxidative stress markers (lipid peroxides, protein carbonyls), and mtDNA deletions in mitochondrial complexes I and IV.
- Selegiline treatment did not affect MDMA-induced hyperthermia but significantly reversed the oxidative stress markers and mtDNA damage.
- Protein expression related to mitochondrial function was also restored by selegiline.
Conclusions:
- MDMA-induced neurotoxicity involves significant mitochondrial damage and oxidative stress in the adolescent rat brain.
- MAO-B activity contributes to MDMA neurotoxicity, as its inhibition by selegiline ameliorates mitochondrial damage.
- Targeting MAO-B may represent a potential therapeutic strategy to mitigate MDMA-induced neurotoxicity.
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