MDMA and Glutamate: Implications for Hippocampal Neurotoxicity

John H. Anneken, Stuart A. Collins, Bryan Yamamoto, Gary A. Gudelsky

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative commonly abused for its psychotropic and mood-elevating effects. These subjective effects are primarily mediated by a release of serotonin and dopamine. MDMA is also known to elicit prolonged toxic effects toward serotonergic nerve terminals, and more recently, has been shown to reduce the number of gamma-aminobutyric acid (GABA) neurons in the hippocampus of rats. In this chapter, this novel GABAergic toxicity and the potential underlying mechanisms are discussed in detail. The primary mechanism presented here is glutamate excitotoxicity, as MDMA has been shown to promote excessive glutamate release specifically in the hippocampus, and the glutamate receptors expressed by GABA neurons in this brain region are especially vulnerable to overstimulation. If conclusively linked by further studies, glutamate signaling and GABA toxicity may provide a mechanism for the observed cognitive impairments and increased seizure vulnerability evoked by MDMA exposure.

Original languageEnglish (US)
Title of host publicationStimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects
PublisherElsevier Inc.
Pages406-414
Number of pages9
Volume2
ISBN (Electronic)9780128003756
ISBN (Print)9780128002124
DOIs
StatePublished - Apr 15 2016
Externally publishedYes

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Keywords

  • Cyclooxygenase
  • GABA
  • Glutamate
  • Hippocampus
  • MDMA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Anneken, J. H., Collins, S. A., Yamamoto, B., & Gudelsky, G. A. (2016). MDMA and Glutamate: Implications for Hippocampal Neurotoxicity. In Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects (Vol. 2, pp. 406-414). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-800212-4.00038-8