POSSIBLE INVOLVEMENT OF NITRIC-OXIDE IN QUINOLINIC ACID-INDUCED CONVULSION IN MICE

Quinolinic acid (QA) induced clonic and tonic convulsions in mice when it was injected into the cerebral ventricle. Pretreatment with L-argi nine (L-Arg), a substrate of nitric oxide (NO) synthase (NOS), and/or 5,6,7,8-tetrahydrobiopterin (THB), a cofactor of NOS, tended to potent iate QA-induced convulsion. N-G-monomethyl-L-arginine (NMMA), a compet itive NOS inhibitor, diminished QA-induced convulsion. This effect of NMMA was attenuated by coadministration of L-Arg or THB. Sodium nitrop russide (SNP), which spontaneously releases NO, did not potentiate, bu t diminished QA-induced convulsion. These findings suggest that an end ogenous NO may be involved, at least in part, in QA-induced convulsion in mice, and that an exogenous NO released from SNP may cause downreg ulation of N-methyl-D-aspartate (NMDA) receptor activity, and thereby prevent the excessive excitation of NMDA receptors and subsequent conv ulsion caused by QA.