Ghrelin, a gastric
peptide with key action on food intake, has been recently recognized as a potential
antiepileptic agent. In the present study, we investigated the involvement of
nitric oxide in the effect of
ghrelin on
penicillin-induced epileptiform activity in rat. Thirty minutes after
penicillin injection,
ghrelin, at doses of 0.5, 1, 2 microg, was administered intracerebroventricularly (i.c.v.).
Ghrelin, at a dose of 1 microg, significantly decreased the mean frequency of epileptiform activity without changing the amplitude whereas other doses of
ghrelin (0.5 and 2 microg) did not alter either the mean of frequency or amplitude of epileptiform activity. The effects of systemic administration of
nitric oxide synthase (NOS) inhibitors, non-selective
N(G)-nitro-l-arginine methyl ester (
l-NAME), selective neuronal NOS inhibitor,
7-nitroindazole (7-NI) and NO substrate,
l-arginine on the anticonvulsive effects of
ghrelin were investigated. The administration of
l-NAME (60 mg/kg, i.p.), 15 min before
ghrelin (1microg) application, reversed the anti-epileptiform effects of
ghrelin whereas 7-NI (40 mg/kg, i.p.) did not influence it. The present study provides electrophysiological evidence that the intracerebroventricular injection of
ghrelin has an inhibitory effect against epileptiform activity in the
penicillin model of
epilepsy. The anti-epileptiform activity of
ghrelin was reversed by nonspecific
nitric oxide synthase inhibitor
l-NAME, but not selective
neuronal nitric oxide synthase inhibitor 7-NI, indicating that
ghrelin requires activation of endothelial-NOS/NO route in the brain.