Quinolinic acid but not MK-801 protects the dopaminergic system from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in goldfish retina

Neurochem Int. 1994 Jun;24(6):559-64. doi: 10.1016/0197-0186(94)90008-6.

Abstract

The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravitreally injected in goldfish eye, involves interplexiform retinal neurons and depletes tyrosine hydroxylase immunoreactivity and dopamine levels. This induced neurotoxicity was prevented by the concomitant administration in non-toxic doses (10 micrograms) of quinolinic acid, an endogenous structural analogue of N-methyl D-aspartate with excitotoxic properties. Quinolinic acid is ineffective on the retinal degeneration induced by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolinic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MK-801, a noncompetitive antagonist of glutamate NMDA-receptors, exerts partial protective effects on MPTP-induced delayed toxicity in mammals. In the goldfish eye, MK-801, injected in low concentration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 1-methyl-4-phenylpyridinium ion, did not prevent retinal neurodegeneration. Ten micrograms of MK-801 alone did not affect retinal neurons, while a higher concentration (20 micrograms) causes the chromatolysis of some photoreceptor nuclei.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors
  • 1-Methyl-4-phenylpyridinium / pharmacology
  • Animals
  • Chromatography, High Pressure Liquid
  • Dizocilpine Maleate / pharmacology*
  • Dopamine / metabolism*
  • Goldfish
  • MPTP Poisoning*
  • Microscopy, Electron
  • Necrosis
  • Neurons / drug effects
  • Neurons / pathology*
  • Neurons / ultrastructure
  • Photoreceptor Cells / drug effects
  • Photoreceptor Cells / pathology
  • Photoreceptor Cells / ultrastructure
  • Quinolinic Acid / pharmacology*
  • Retina / drug effects
  • Retina / pathology*

Substances

  • Dizocilpine Maleate
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Quinolinic Acid
  • 1-Methyl-4-phenylpyridinium
  • Dopamine