Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats

Daiken Han, Kiyofumi Yamada, Kouji Senzaki, Huabao Xiong, Hiroyuki Nawa, Toshitaka Nabeshima

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52 Scopus citations


We investigated the role of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in the pentylenetetrazole (PTZ)-induced kindling in rats. Seizures were induced by single administration of PTZ, which was associated with an increase in levels of NO metabolites (NO(x)) in the hippocampus. Pretreatment with a neuronal NO synthase inhibitor, 7- nitroindazole (7-NI), diminished the PTZ-induced increase in NO(x) levels without affecting the seizure intensity. Repeated administration of PTZ produced a gradual increase in the seizure intensity, leading to the development of kindling. In the kindled rats, PTZ at a dose of 40 mg/kg increased NO(x) 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 NO(x) levels. A significant increase in BDNF levels was observed in the hippocampus of the kindled rats, which returned to the control levels following seizures induced by PTZ. 7-NI reduced the hippocampal BDNF levels in control 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.

Original languageEnglish
Pages (from-to)792-798
Number of pages7
JournalJournal of Neurochemistry
Issue number2
StatePublished - 2000
Externally publishedYes


  • 7-Nitro-indazole
  • Brain- derived neurotrophic factor
  • In vivo microdialysis
  • Kindling
  • Nitric oxide
  • Pentylenetetrazole


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