Kainic acid may enhance hippocampal NO generation of awake rats in a seizure stage-related fashion.

Temporal changes in kainate-induced seizure activity and hippocampal NO generation were evaluated simultaneously in conscious rats by using in vivo microdialysis and by determining the concentrations of nitrite and nitrate in perfusates. Intraperitoneal injection of kainic acid produced 'wet dog shake', focal seizure of the limbs and neck, hypersalivation, or generalized convulsion. These behavioral changes peaked at 120 min after the drug challenge and lasted for about 100 min. In contrast, the concentrations of NO metabolites, nitrite and nitrate, in the hippocampal perfusates increased rapidly and reached a plateau level at 40 min after the injection, and the level remained high for over 220 min. The increase was more marked in animals presenting severe seizures than those presenting mild ones. Pre-treatment with 25 mg/kg N(G)-nitro-L-arginine methyl ester promoted the severity of kainate-induced seizures, but it suppressed the increase in NO metabolites. These results suggest that kainic acid enhances hippocampal NO generation in a severity-related manner of the induced seizures. The enhanced NO generation upon kainate challenge appears mainly to be involved in seizure suppression.