MK‐801 Fails to Protect Against the Dopaminergic Neuropathology Produced by Systemic 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Mice or Intranigral 1‐Methyl‐4‐Phenylpyridinium in Rats

Patricia K. Sonsalla, Gail D. Zeevalk, Lawrence Manzino, Andrew Giovanni, William J. Nicklas

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103 Scopus citations

Abstract

Abstract: Previous studies from this laboratory demonstrated that (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine maleate (MK‐801), an N‐methyl‐D‐aspartate (NMDA) receptor antagonist, did not prevent neurotoxicity to dopaminergic neurons in mice produced by systemic treatment with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). However, Turski et al. [Nature349, 414–418 (1991)] reported that extended treatment of rats with NMDA receptor antagonists (six injections at 4‐h intervals) did prevent the loss of nigral dopaminergic neurons resulting from an intranigral infusion of 1‐methyl‐4‐phenylpyridinium (MPP+), the neurotoxic metabolite of MPTP. The present studies examined if a similar extended treatment with MK‐801 would protect mice from the neurotoxicity of systemically administered MPTP. Six intraperitoneal injections of MK‐801 given at 4‐h intervals did not protect mice against the MPTP‐induced neostriatal dopamine loss measured 1 week after treatment. In other experiments, designed to replicate and expand on the results of Turski et al. (1991), the extended treatment of rats with MK‐801 did not prevent MPP+‐induced cell loss in the infused substantia nigra pars compacta or the dopamine depletion in the ipsilateral neostriatum at 7‐11 days after MPP+ infusion. These results do not support the hypothesis that NMDA receptors are involved with MPTP/MPP+‐induced neurodegeneration.

Original languageEnglish (US)
Pages (from-to)1979-1982
Number of pages4
JournalJournal of neurochemistry
Volume58
Issue number5
DOIs
StatePublished - May 1992

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • 1‐Methyl‐4‐phenylpyridinium
  • 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine
  • Excitotoxicity
  • MK‐801
  • N‐Methyl‐D‐aspartate receptors
  • Parkinson's disease

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