QUINOLINIC ACID BUT NOT MK-801 PROTECTS THE DOPAMINERGIC SYSTEM FROM METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED TOXICITY IN GOLDFISH RETINA

The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravit really injected in goldfish eye, involves interplexiform retinal neuro ns and depletes tyrosine hydroxylase immunoreactivity and dopamine lev els. This induced neurotoxicity was prevented by the concomitant admin istration in nontoxic doses (10 mu g) of quinolinic acid, an endogenou s structural analogue of N-methyl D-aspartate with excitotoxic propert ies. Quinolinic acid is ineffective on the retinal degeneration induce d by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolin ic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl-1,2,3,6-tetr ahydropyridine. MK-801, a noncompetitive antagonist of glutamale NMDA- receptors, exerts partial protective effects on MPTP-induced delayed t oxicity in mammals. In the goldfish eye, MK-801, injected in low conce ntration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine or 1-methyl-4-phenylpyridinium ion, did not prevent retinal n eurodegeneration. Ten mu g of MK-801 alone did not affect retinal neur ons, while a higher concentration (20 mu g) causes the chromatolysis o f some photoreceptor nuclei.