Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats

We investigated the role of nitric oxide (NO) and brain-derived neurotrophi c factor (BDNF) in the pentylenetetrazole (PTZ)-induced kindling in rats. S eizures were induced by single administration of PTZ, which was associated with an increase in levels of NO metabolites (NOx) in the hippocampus. Pret reatment with a neuronal NO synthase inhibitor, 7-nitroindazole (7-NI), dim inished the PTZ-induced increase in NOx levels without affecting the seizur e intensity. Repeated administration of PTZ produced a gradual increase in the seizure intensity, leading to the development of kindling. In the kindl ed rats, PTZ at a dose of 40 mg/kg increased NOx levels in the hippocampus, whereas it had no effect in control animals. Cotreatment of 7-NI with PTZ blocked the development of kindling and attenuated the PTZ-induced increase in NOx levels. A significant increase in BDNF levels was observed in the h ippocampus of the kindled rats, which returned to the control levels follow ing seizures induced by PTZ, 7-NI reduced the hippocampal BDNF levels in co ntrol rats and suppressed the increase of BDNF levels in the kindled rats. Our findings suggest that NO plays a role in the development of PTZ-induced kindling and that BDNF may contribute to the NO-dependent plastic changes in neuronal excitability.