This study aimed to examine whether celecoxib influences clonic seizure thresholds through modulation of nitric oxidergic (NO) pathway. The effect of celecoxib (1-5 mg/kg, p.o.) was investigated on clonic seizures induced by pentylenetetrazole (PTZ, 50 and 80 mg/kg, i.p.) in male Swiss mice. The interaction of celecoxib-induced effects with NO pathway was examined using a NO synthase (NOS) inhibitor, N(G)-omega-nitro-L-arginine methyl ester (L-NAME, 20 and 50 mg/kg, i.p.) and a NOS substrate, L-arginine (100 and 200 mg/kg, i.p.). The criteria for the development of seizure activity were the possibility for appearance of generalized clonus and prolongation of latency to the onset of convulsions following administration of 50 and 80 mg/kg of PTZ, respectively. Pretreatment with celecoxib (2.5 and 5 mg/kg) or L-NAME (50 mg/ kg) induced anticonvulsant effect on the PTZ-induced clonic seizures. L-arginine at the dose of 200 mg/kg had proconvnlsant effect. A sub-effective dose of celecoxib (1 mg/kg) induced an additive anticonvulsant effect when co-administered with L-NAME (20 mg/kg). Although L-arginine (100 mg/kg) per se did not influence PTZ-induced convulsion, it could attenuate the anticonvulsant effect of celecoxib (5 mg/kg). Our results indicate that celecoxib induces an anticonvulsant effect on clonic seizure threshold that may involve NO pathway.
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