Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice

The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 μg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 μg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice. In addition, the antiseizure effect of L-arginine was blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine (NOARG) and the NO scavenger, hemoglobin, while the effect of sodium nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the antiseizure effect of L-arginine, but not that of sodium nitroprusside, is mediated by NO production resulting from the activation of NO synthase. Therefore, a decrease in the NO production via NO synthase may be involved in the hypersusceptibility to pentylenetetrazole during diazepam withdrawal.