ROLE OF NITRIC-OXIDE IN THE HYPERSUSCEPTIBILITY TO PENTYLENETETRAZOLE-INDUCED SEIZURE IN DIAZEPAM-WITHDRAWN MICE

The decrease in the seizure threshold for pentylenetetrazole in diazep am-withdrawn mice was not significantly affected by L-arginine (50 and 100 mu g/mouse, i.c.v.), which did have an antiseizure effect in chro nically vehicle-treated mice. Sodium nitroprusside (25 and 50 mu g/mou se, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice.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 nitr ic oxide (NO) synthase inhibitor, N-nitro-L-arginine (NOARG) and the N O scavenger, hemoglobin, while the effect of sodium nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the antisei zure effect of L-arginine, but not that of sodium nitroprusside, is me diated by NO production resulting from the activation of NO synthase. Therefore, a decrease in the NO production via NO synthase may be invo lved in the hypersusceptibility to pentylenetetrazole during diazepam withdrawal. (C) 1998 Elsevier Science B.V.