leptin and 7-nitroindazole

The aim of the present study was to investigate the role of NO as a mediator of leptin action at the penicillin-induced epileptiform activity in rat. Thirty minutes after penicillin injection, leptin, at a dose of 1 microg, significantly increased the mean frequency of epileptiform activity without changing the amplitude. The effects of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO precursor, L-arginine on the effects of leptin were investigated. The occurrence of anticonvulsant activity of 7-NI (40 mg/kg, i.p.) was significantly delayed in the presence of leptin (1 microg). The administration of L-NAME (60 mg/kg, i.p.), 30 min before leptin (1 microg) application, did not influence proconvulsant activity of leptin. The administration of L-arginine (1000 mg/kg, i.p.) 30 min before the effective dose of leptin (1 microg, i.c.v.) reversed the proconvulsant effects of leptin whereas the same dose of its inactive enantiomer, D-arginine (1000 mg/kg, i.p.) failed to influence the proconvulsant effect of leptin. The electrophysiological evidence of the present study suggests that neuronal NOS/NO pathway is involved in mediating leptin effects on penicillin-induced epileptiform activity.

Topics: Animals; Anticonvulsants; Arginine; Brain; Convulsants; Electroencephalography; Enzyme Inhibitors; Indazoles; Leptin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Penicillins; Rats; Rats, Wistar; Seizures; Signal Transduction