Involvement of Nitric Oxide in Pentylenetetrazole‐Induced Kindling in Rats

• Published in: Journal of neurochemistry 2000-02, Vol.74 (2), p.792-798
• Main Authors: Han, Daiken, Yamada, Kiyofumi, Senzaki, Kouji, Xiong, Huabao, Nawa, Hiroyuki, Nabeshima, Toshitaka
• Format: Article
• Language: English
• Subjects: 7‐Nitroindazole; Animals; Biological and medical sciences; Brain-Derived Neurotrophic Factor - metabolism; Brain‐derived neurotrophic factor; Convulsants - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - drug effects; Hippocampus - metabolism; In vivo microdialysis; Kindling; Kindling, Neurologic - physiology; Male; Medical sciences; Nerve Growth Factor - metabolism; Nervous system (semeiology, syndromes); Neurology; Nitrates - metabolism; Nitric oxide; Nitric Oxide - physiology; Nitrites - metabolism; Pentylenetetrazole; Pentylenetetrazole - pharmacology; Rats; Rats, Wistar; Seizures - chemically induced
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.740792.x

: 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.