MODIFICATION OF KAINATE-INDUCED BEHAVIORAL AND ELECTROGRAPHIC SEIZURES FOLLOWING INHIBITION OF NITRIC-OXIDE SYNTHASE IN MICE

We assessed the effects of N-omega-nitro-L-arginine-methyl ester (L-NA ME), an inhibitor of nitric oxide synthase (NOS), on behavioral and el ectrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effect s of kainate (44 mg/kg s.c.), transforming long-latency clonic convuls ions into short-latency fits of wild-running, and increased the incide nce of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced ep ileptiform afterdischarge recorded via electrodes chronically implante d into the hippocampus, amygdala, frontal cortex or mesencephalic reti cular formation (Expt. 2). We also observed a dramatic uncoupling of b ehavioral and electrographic seizures in mice treated with L-NAME 30 m in prior to kainate: 4/6 mice treated with L-NAME failed to express af terdischarge from any of the sites assessed during fits of wild-runnin g. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter beh avioral (clonic) or electrographic seizures elicited by intrahippocamp al kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-run ning following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose o f systemic kainate required for either clonic convulsions or wild-runn ing (Expt. 5), The observations that L-NAME potentiates kainate-induce d wild-running but not necessarily clonus suggest the involvement of t ectopontine mechanisms.