Journal of Neuroimmune Pharmacology

, Volume 8, Issue 1, pp 58–65 | Cite as

MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase

  • John H. Anneken
  • Jacobi I. Cunningham
  • Stuart A. Collins
  • Bryan K. Yamamoto
  • Gary A. GudelskyEmail author


3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus . Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.


MDMA Glutamate Cyclooxygenase GABA 



This work was supported by awards from the National Institute on Drug Abuse DA 07427 (GG) and DA016886 (BY).

Conflict of Interest

The authors declare no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • John H. Anneken
    • 1
  • Jacobi I. Cunningham
    • 2
  • Stuart A. Collins
    • 2
  • Bryan K. Yamamoto
    • 2
  • Gary A. Gudelsky
    • 1
    Email author
  1. 1.James Winkle College of PharmacyUniversity of CincinnatiCincinnatiUSA
  2. 2.Department of NeurosciencesUniversity of Toledo College of MedicineToledoUSA

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