Interaction of Leptin and Nitric Oxide Pathway on Penicillin-Induced Epileptiform Activity in Rats

Abstract

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 μg, 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 μg). The administration of L-NAME (60 mg/kg, i.p.), 30 min before leptin (1 μg) 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 μg, 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. © 2010 Elsevier B.V. All rights reserved.