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 stimulant drug MDMA (Ecstasy) increases dopamine transmission in the nucleus accumbens, a brain region involved in reward. This study in male rats examined how the two mirror-image forms (enantiomers) of MDMA—S(+)-MDMA and R(−)-MDMA—affect dopamine release and a downstream signaling molecule called phosphorylated ERK (pERK) in the shell and core of the nucleus accumbens. Racemic MDMA (the standard mixture) and S(+)-MDMA increased dopamine and pERK levels in a dose-related way, with S(+)-MDMA being more potent. R(−)-MDMA had no effect. Blocking D1 dopamine receptors prevented the pERK increase, while blocking D2/D3 receptors did not. The results indicate that the S(+) enantiomer drives MDMA's dopamine-stimulating effects, and pERK serves as a marker of D1-receptor-mediated dopamine signaling.
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.