Opioid receptor antagonist nalmefene stereospecifically inhibits glutamate release during global cerebral ischemia

S. H. Graham, H. Shimizu, A. Newman, P. Weinstein, A. I. Faden

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The opioid receptor antagonist nalmefene improves cellular bioenergetics and attenuates the reduction in tissue glutamate levels after global cerebral ischemia/reperfusion. The latter finding suggests that nalmefene might inhibit glutamate release during ischemia. To test this hypothesis, we used microdialysis techniques to examine the effect of nalmefene pretreatment on extracellular excitatory amino acid levels during global cerebral ischemia in rats. Saline, (-)-nalmefene (20, 100 or 500 μg/kg) or the inactive nalmefene enantiomer (+)-nalmefene (100 μg/kg) were given 15 min prior to induction of ischemia using a multi-vessel occlusion model. Pretreatment with (-)-nalmefene decreased peak dialysate glutamate in a dose-dependent fashion as compared to saline-treated controls, whereas (+)-nalmefene had no effect. These results suggest that opioid receptors may modulate glutamate release during ischemia and that inhibition of excitatory amino acid release may contribute to the protective actions of opioid receptor antagonists in cerebral ischemia.

Original languageEnglish
Pages (from-to)346-350
Number of pages5
JournalBrain research
Volume632
Issue number1-2
DOIs
Publication statusPublished - 1993 Dec 31

Keywords

  • Excitatory amino acid
  • Microdialysis
  • Opioid antagonist
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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