Chronic administration of MDMA (ecstasy) during late adolescence in mice worsens the brain damage caused by MPTP, a toxin that induces Parkinson's disease (PD) in humans. Mice treated twice daily with MDMA (10 mg/kg) from 8 to 17 weeks of age, then given MPTP (20 mg/kg four times), showed greater activation of microglia and astroglia in the striatum and substantia nigra pars compacta (SNc) compared to mice given only MPTP or vehicle. This neuroinflammation was accompanied by a greater loss of dopamine-producing neurons (indicated by reduced tyrosine hydroxylase immunoreactivity) in the SNc and striatum. The findings suggest that MDMA use may increase the risk of dopaminergic neuron degeneration.
The S(+) enantiomer of MDMA, but not the R(−) enantiomer, activates microglia and astroglia in the mouse striatum, though less strongly than racemic MDMA. Combining both enantiomers produces no greater activation than S(+) alone. Only racemic MDMA slightly activates microglia in other brain regions. S(+) and racemic MDMA similarly increase motor activity and body temperature, while R(−) has no effect. Body temperature rise correlates with glial activation. The findings indicate additive rather than synergistic effects of the two enantiomers and highlight the need to study their separate contributions to MDMA's neuroinflammatory and neurotoxic effects.