Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats.
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 (NOx) in the hippocampus. Pretreatment with a neuronal NO synthase inhibitor, 7-nitroindazole (7-NI), diminished the PTZ-induced increase in NOx 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 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 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.
Han
D
D
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan.
Yamada
K
K
Senzaki
K
K
Xiong
H
H
Nawa
H
H
Nabeshima
T
T
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced
D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D010433:Pentylenetetrazole