Evidence for an involvement of nitric oxide and gamma aminobutyric acid in the anticonvulsant action of L-arginine on picrotoxin-induced convulsions in rats.

Five, 30, and 60 min pretreatment of 1000 mg/kg and not 500 mg/kg of L-arginine inhibited convulsions induced by picrotoxin. The concentrations of nitric oxide (NO) and gamma aminobutyric acid (GABA) were increased in the brain 5, 30, and 60 min after administration of 1000 mg/kg and not 500 mg/kg of L-arginine. A much higher dose of L-arginine (2000 mg/kg), 30 min after administration, produced a lesser anticonvulsant and NO and GABA increasing actions as compared to that produced by 1000 mg/kg of L-arginine. The same dose of L-arginine, 60 min after administration, decreased the concentrations of both NO and GABA and increased the convulsion frequency of picrotoxin. An NO decreasing dose of nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) decreased brain GABA concentration and increased the convulsant action of picrotoxin. Further, L-NAME pretreatment prevented L-arginine (1000 mg/kg) from producing anticonvulsant and NO and GABA increasing effects. An interpretation of these results suggests that NO synthesized from systemically administered L-arginine inhibits convulsions by increasing the concentration of GABA in the brain. However, the effects of L-arginine are reversible, if it is administered at a higher dose (2000 mg/kg) 60 min prior to the test. It is concluded that L-arginine produces anticonvulsant or proconvulsant action depending upon the dose and time of its administration-related changes in the concentrations of NO and GABA in the brain.