The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats

The majority of experimental and clinical studies show that ghrelin and cannabinoids are potent inhibitors of epileptic activity in various models of epilepsy. A number of studies have attempted to understand the connection between ghrelin and cannabinoid signalling in the regulation of food intake. Since no data show a functional interaction between ghrelin and cannabinoids in epilepsy, we examined the relationship between these systems via penicillin-induced epileptiform activity in rats. Doses of the CBI receptor agonist arachidony1-2-chloroethylamide (ACEA) (2.5 and 7.5 mu g), the CB1 receptor antagonist N-(piperidinl-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM-251) (0.25 and 0.5 mu g) and ghrelin (0.5 and 1 mu g) were administered intracerebroventricularly (i.c.v.) 30 minutes after the intracortical (i.c.) application of penicillin. In the interaction groups, the animals received either an effective dose of ACEA (7.5 mu g, i.c.v.) or a non-effective dose of ACEA (2.5 mu g, i.c.v.) or effective doses of AM-251 (0.25, 0.5 mu g, i.c.v.) 10 minutes after ghrelin application. A1 mu g dose of ghrelin suppressed penicillin-induced epileptiform activity. The administration of a 0.25 mu g dose of AM-251 increased the frequency of penicillin-induced epileptiform activity by producing status epilepticus-like activity. A 7.5 mu g dose of ACEA decreased the frequency of epileptiform activity, whereas a non-effective dose of ACEA (2.5 mu g) did not change it. Effective doses of AM-251 (0.25, 0.5 mu g) reversed the ghrelin's anticonvulsant activity. The application of non-effective doses of ACEA (2.5 mu g) together with ghrelin (0.5 mu g) within 10 minutes caused anticonvulsant activity, which was reversed by the administration of AM-251 (0.25 mu g). The electrophysiological evidence from this study suggests a possible interaction between ghrelin and cannabinoid CB1 receptors in the experimental model of epilepsy. (C) 2014 Elsevier Ltd. All rights reserved.