Nitric Oxide Synthase Inhibitors Differently Affect Nicotine-induced Convulsions in Mice

The aim of this study was to investigate the role of nitric oxide (NO), a second messenger and/or a neurotransmitter, in convulsions induced by nicotine. We examined the effects of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine (NNA), a non -selective NOS inhibitor, and aminoguanidine, a selective inducible NOS inhibitor, on convulsions induced by intraperitoneally (ip) administered nicotine in mice. 7-NI, at the doses of 50 and 100 mg/kg ip; 30 min before nicotine), dose-dependently reduced the CD'# of nicotine (the dose of convulsant producing seizures in 50% of mice) from 6.7 to 5.2 (p < 0.05) and 3.7 (p < 0.001) mg/kg, respectively. L-arginine (L-Arg), a NO precursor, at a dose of 500 mg/kg ip, which itself had no effect on the CD'# of nicotine, did not reverse the proconvulsant effect of 7-NI. Lower doses of 7-NI (12.5 and 25 mg/kg) had no effect on convulsions. NNA, at a dose of 40 mg/kg (ip; 30 min before nicotine), dose-dependently increased the CD'# of nicotine from 6.7 to 9.3 (p < 0.001) mg/kg. The anticonvulsant effect of NNA was reversed by L-Arg (500 mg/kg) with the nicotine CD'# being 7.1 mg/kg (p < 0.001 vs. NNA given alone). Lower dose of NNA (1 mg/kg) did not change significantly the CD'# value. Aminoguanidine administered at a dose of 100 mg/kg (ip; 15 and 30 min before nicotine) did not affect convulsions. The results indicate that in nicotine-induced convulsions: 1) 7-NI is a proconvulsant and its effect does not appear to result only from the impaired NO synthesis, 2) NNA is an anticonvulsant acting most likely via L-Arg-NO pathway, 3) aminoguanidine has no effect on convulsions. This work adds more new data to existing evidence that suggest different action of NOS inhibitors in chemically induced convulsions in animals.