The N‐Methyl‐D‐Aspartate Antagonist MK‐801 Fails to Protect Dopaminergic Neurons from 1‐Methyl‐4‐ Phenylpyridinium Toxicity In Vitro

Francoise Finiels‐Marlier, Ann M. Marini, Pat Williams, Steven M. Paul

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Abstract: Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuroprotective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK‐801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK‐801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA‐induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor.

Original languageEnglish
Pages (from-to)1968-1971
Number of pages4
JournalJournal of Neurochemistry
Volume60
Issue number5
DOIs
StatePublished - May 1993
Externally publishedYes

Keywords

  • 1‐Methyl‐4‐phenylpyridinium
  • Dopaminergic neurons
  • MK‐801
  • Mesencephalic cultures
  • N′‐Methyl‐D‐aspartate receptor

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