title: MDMA administration during adolescence exacerbates MPTP-induced cognitive impairment and neuroinflammation in the hippocampus and prefrontal cortex.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Costa
authors.forename: Nicola
authors.initials: N
authors.lastname: Simola
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020267:MPTP Poisoning / Q000150:complications*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D018817:N-Methyl-3,4-methylenedioxyamphetamine