, Volume 231, Issue 20, pp 4007–4018

MDMA administration during adolescence exacerbates MPTP-induced cognitive impairment and neuroinflammation in the hippocampus and prefrontal cortex

Original Investigation

DOI: 10.1007/s00213-014-3536-z

Cite this article as:
Costa, G., Simola, N. & Morelli, M. Psychopharmacology (2014) 231: 4007. doi:10.1007/s00213-014-3536-z



We have recently shown that chronic exposure to 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) of adolescent mice exacerbates dopamine neurotoxicity and neuroinflammatory effects elicited by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the substantia nigra and striatum at adulthood.


The present study investigated whether the amplification of MPTP effects by previous treatment with MDMA extends to the limbic and cortical regions and consequently affects cognitive performance.


Mice received MDMA (10 mg/kg, twice a day/twice a week) for 9 weeks, followed by MPTP (20 mg/kg × 4 administrations), starting 2 weeks after MDMA discontinuation. Complement type 3 receptor (CD11b) and glial fibrillary acidic protein (GFAP) were evaluated by immunohistochemistry in both the hippocampus and the medial prefrontal cortex (mPFC) to measure microglia and astroglia activation. These neurochemical evaluations were paired with an assessment of cognitive performance by means of the novel object recognition (NOR) and spontaneous alternation tasks.


MPTP administration to MDMA-pretreated mice elicited a stronger activation of CD11b and GFAP in both the hippocampus and the mPFC compared with either substance administered alone. Furthermore, NOR performance was lower in MDMA-pretreated mice administered MPTP compared with mice that received either substance alone.


These results demonstrate that MDMA–MPTP negative interactions extend to the limbic and cortical regions and may result in cognitive impairment, providing further evidence that exposure to MDMA may amplify the effects of later neurotoxic insults.


Amphetamines Astroglia CD11b Dopamine Drug of abuse Ecstasy GFAP Microglia Novel object recognition task Spontaneous alternation 

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Giulia Costa
    • 1
  • Nicola Simola
    • 1
  • Micaela Morelli
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Biomedical Sciences, Section of NeuropsychopharmacologyUniversity of CagliariCagliariItaly
  2. 2.Centre of Excellence for Neurobiology of DependenceUniversity of CagliariCagliariItaly
  3. 3.National Research Council (CNR) Neuroscience InstituteCagliariItaly
  4. 4.National Institute of Neuroscience (INN)University of CagliariCagliariItaly

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