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

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An Erratum to this article was published on 28 October 2014

Abstract

Rationale

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.

Objectives

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.

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Acknowledgments

This study was supported by funds from Regione Autonoma della Sardegna (Legge Regionale 7 Agosto 2007, N.7, annualità 2008 and 2010). Dr. Giulia Costa gratefully acknowledges the Sardinian Regional Government for financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013–Axis IV Human Resources, Line of Activity l.3.1 “Finanziamento ai corsi di dottorato finalizzati alla formazione di capitale umano altamente specializzato”). Dr. Nicola Simola gratefully acknowledges the Sardinian Regional Government for financial support (P.O.R. Sardegna F.S.E. Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2007–2013 – Axis IV Human Resources, Objective l.3, Line of Activity l.3.1 “Avviso di chiamata per il finanziamento di Assegni di Ricerca”).

The authors are grateful to Prof. Antonio Plumitallo and Mr. Renato Mascia, Department of Life and Environmental Sciences, University of Cagliari, for their help with the MDMA synthesis.

Conflicts of interest

Nothing to report.

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). Dr. Giulia Costa and Dr. Nicola Simola were supported by funds from Regione Autonoma della Sardegna (P.O.R. FSE 2007–2013).

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Authors and Affiliations

  1. Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Giulia Costa, Nicola Simola & Micaela Morelli

  2. Centre of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari, Italy

    Micaela Morelli

  3. National Research Council (CNR) Neuroscience Institute, Cagliari, Italy

    Micaela Morelli

  4. National Institute of Neuroscience (INN), University of Cagliari, Cagliari, Italy

    Micaela Morelli

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  1. Giulia Costa
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Correspondence to Micaela Morelli.

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Costa, G., Simola, N. & Morelli, M. MDMA administration during adolescence exacerbates MPTP-induced cognitive impairment and neuroinflammation in the hippocampus and prefrontal cortex. Psychopharmacology 231, 4007–4018 (2014). https://doi.org/10.1007/s00213-014-3536-z

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