PICOLINIC-ACID PROTECTS AGAINST QUINOLINIC ACID-INDUCED DEPLETION OF NADPH DIAPHORASE CONTAINING NEURONS IN THE RAT STRIATUM

Previous studies in our laboratory have demonstrated that focal inject ions of picolinic acid (PIG) protect the cholinergic neurons of the nu cleus basalis magnocellularis (nbm) against quinolinic acid (QUIN)-ind uced neurotoxicity. The present study was designed to examine the effe cts of chronic infusions of QUIN and PIC on nicotinamide adenine dinuc leotide (NADPH) diaphorase containing neurons of the rat striatum. Usi ng osmotic minipumps, QUIN (6 nmol/h) and PIC (18 nmol/h) were infused alone or in combination to examine the neurotoxic effects of QUIN and the potential anti-neurotoxic action of PIG. Exposure to QUIN for 7 d ays severely depleted NADPH diaphorase-positive neurons. When co-infus ed with this neurotoxic dose of QUIN, PIC attenuated the depletion of NADPH diaphorase neurons induced by QUIN. The infusion of PIC alone di d not affect the number of these neurons. These results indicate that PIC itself is not neurotoxic and effectively prevents chronic QUIN-ind uced neurotoxicity in the rat striatum. Since PIC and QUIN are derived from the same metabolic pathway, a balance between endogenous compoun ds that produce neurotoxicity and those antagonizing these effects may be important in normal neuronal function.