Effects of sodium nitroprusside, a nitric oxide donor, on gamma-aminobutyric acid concentration in the brain and on picrotoxin-induced convulsions in combination with phenobarbitone in rats

The concentrations of nitric oxide (NO), the neuronal messenger molecule, and gamma-aminobutyric acid (GABA), the inhibitory neurotransmitter, and the activity of gamma-aminobutyric acid transaminase (GABA-T), the enzyme involved in the degradation of GABA, were measured in the brain of rats treated with graded doses (1.25, 2.5, 5.0 mg/kg) of sodium nitroprusside (SNP), the donor of NO. The effect of SNP was tested alone and in combination with phenobarbitone (PB), the GABA potentiating antiepileptic drug, against picrotoxin (PCT) (5 mg/kg)-induced convulsions in rats. The results of these studies showed that NO released from SNP (2.5 mg/kg) had a potential to inhibit GABA-T activity resulting in an increase in the concentration of GABA in the brain. Thus, SNP (2.5 mg/kg) was able to inhibit PCT-induced convulsions and was able to produce an additive anticonvulsant action with PB. However, a much greater increase in the concentration of NO by 5.0 mg/kg of SNP did not change the activity of GABA-T and the concentration of GABA, and promoted the convulsant action of PCT. These results suggest that a moderate increase in the concentration of NO following the administration of its donor SNP (2.5 mg/kg) results in an enhancement of the concentration of GABA in the brain and in an inhibition of PCT-induced convulsions independently and additively with PB and that a marked increase in NO concentration after the administration of a larger dose of SNP (5.0 mg/kg) results in proconvulsant action.