Get access

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

Authors

  • Giulia Costa MS,

    1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy
    Search for more papers by this author
  • Lucia Frau PhD,

    1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy
    Search for more papers by this author
  • Jadwiga Wardas PhD,

    1. Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
    Search for more papers by this author
  • Annalisa Pinna PhD,

    1. National Research Council of Italy, Institute of Neuroscience, Cagliari, Italy
    Search for more papers by this author
  • Antonio Plumitallo MS,

    1. Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy
    Search for more papers by this author
  • Micaela Morelli PhD

    Corresponding author
    1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Cagliari, Italy
    2. Center of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari, Italy
    • Correspondence to: Dr. Micaela Morelli, Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy; morelli@unica.it

    Search for more papers by this author

  • Funding agencies: This study was supported by funds from the Regione Autonoma della Sardegna (Legge Regionale 7 Agosto 2007, N.7, annualità 2008 and 2010), from the Fondazione Banco di Sardegna supporting Dr. Lucia Frau (Rep. 13/19844 del 31-01-2011), and from the Regione Autonoma della Sardegna supporting Dr. Giulia Costa. (P.O.R. FSE 2007–2013).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

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

Ancillary