Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice.
The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 microg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 microg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice.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.
Tsuda
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Shimizu
N
N
Yajima
Y
Y
Suzuki
T
T
Misawa
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003975:Diazepam / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced*; D013375:Substance Withdrawal Syndrome
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D003975:Diazepam; D010433:Pentylenetetrazole