MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice

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.

Study at a glance

Abstract

ABSTRACT Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4‐Methylenedioxymethamphetamine (MDMA; “ecstasy”) is an amphetamine‐related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg × 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle‐treated or vehicle + MPTP‐treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA‐treated mice and with a further decrease in the striatum and the SNc of MDMA + MPTP‐treated mice compared with vehicle‐treated, MDMA‐treated, and MPTP‐treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration. © 2013 International Parkinson and Movement Disorder Society