The effect of nitric oxide synthase inhibition on quinolinic acid toxicity in the rat striatum

Neuroscience
G M MacKenzieC D Marsden

Abstract

Neurons containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and acetylcholinesterase in the striatum are spared in Huntington's disease. It has been claimed that these neurons are also spared after intrastriatal injection of the N-methyl-D-aspartate receptor agonist, quinolinic acid. In the present study the effects of intrastriatal injection of quinolinic acid (15, 30 and 60 nmol) on neurons containing NADPH diaphorase and acetylcholinesterase were examined in rats. Neurons identified histochemically were counted in whole striatal sections at the level of the injection site and at 400 microns intervals anterior and posterior to the injection site. There was a dose-related reduction in the total number of NADPH diaphorase-containing neurons counted in these levels, but only a mild loss of acetylcholinesterase-containing neurons. Acetylcholinesterase-positive neurons were observed near the injection site following administration of all doses. The effects of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (50 mg/kg, i.p. twice daily for seven days), on quinolinic acid (30 nmol. day 5)-induced toxicity were also investigated. Striatal sections were stained for NADPH diaphorase-, ...Continue Reading

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