Quinolinic acid (QA) induced clonic and tonic convulsions in mice when it was injected into the cerebral ventricle. Pretreatment with l-arginine (L-Arg), a substrate of nitric oxide (NO) synthase (NOS), and/or 5,6,7,8-tetrahydrobiopterin (THB), a cofactor of NOS, tended to potentiate QA-induced convulsion. NG-monomethyl-l-arginine (NMMA), a competitive NOS inhibitor, diminished QA-induced convulsion. This effect of NMMA was attenuated by coadministration of L-Arg or THB. Sodium nitroprusside (SNP), which spontaneously releases NO, did not potentiate, but diminished QA-induced convulsion. These findings suggest that an endogenous NO may be involved, at least in part, in QA-induced convulsion in mice, and that an exogenous NO released from SNP may cause downregulation of N-methyl-D-aspartate (NMDA) receptor activity, and thereby prevent the excessive excitation of NMDA receptors and subsequent convulsion caused by QA.
All Science Journal Classification (ASJC) codes
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience