The Role of Nitric Oxide in Seizures Induced by Pentylenetetrazole

Kim, Jun Ho; Kim, Koo Kwan

Abstract

PURPOSE: Nitric oxide(NO) is a highly reactive messenger molecule that is synthesized by nitric oxide synthase(NOS) in a number of tissues including the brain. Our aim was to examine the possible role of NO on pentylenetetrazole(PTZ)-induced seizure in rats as a proconvulsant or an anticonvulsant.
METHODS
Male Sprague-Dawley rats weighing 200-300g were used. PTZ(40mg/kg) was used to induce seizure. In order to examine the role of NO in seizures, the neuronal nitric oxide synthase (nNOS) was blocked by a specific inhibitor, 50mg/kg 7-nitroindazole(7-NI), and a non-specific inhibitor, 50mg/kg L-nitroarginine(L-NA). Both 7-NI and L-NA were administered 30 min before the administration of PTZ. We evaluated the onset time of the first myoclonic jerk and the nature of seizures, such as the types and severity of the seizures in each group. Western blot and RT-PCR were used to examine the expression of nNOS mRNA and proteins in the hippocampus of each group.
RESULTS
The onset time of the first rnyoclonic jerk was markedly delayed in the 7-NI and L-NA pretreated groups in comparison to the PTZ group. In addition, 7-NI and L-NA markedly sup- pressed the severity of PTZ-induced seizure. The expression of nNOS mRNA was higher in the PTZ and 7-NI pretreated groups than in the control group. The expression of nNOS protein was more suppressed in the 7-NI and L-NA pretreated groups than in the PTZ group.
CONCLUSION
The expression of nNOS protein appears to increase in PTZ-induced seizures. Both specific and non-specific NOS inhibitors produce a reduction in seizure activity and nNOS protein expression. These results suggest that nNOS may be in a close relationship with seizures, and NO may play an important role as a proconvulsant in the PTZ-induced seizure in rats.