The Role of CB1‐Receptors in the Proconvulsant Effect of Leptin on Penicillin‐Induced Epileptiform Activity in Rats

Abstract

Prior studies have demonstrated the involvement of leptin and cannabinoids in food intake and metabolism. However, the interaction between leptin and cannabinoids in epilepsy has not been studied. This study elucidated the relationship between leptin and cannabinoids in penicillin-induced epileptiform activity in rats. The CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA), at doses of 2.5 and 7.5 μg, the CB1 receptor antagonist, [N-(piperidine-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide] (AM-251), at doses of 0.125 and 0.25 μg, and leptin, at the dose of 1 μg, were administered intracerebroventricularly (i.c.v.) 30 min after intracortical penicillin (i.c.) application. Leptin caused proconvulsant activity in all groups. The administration of AM-251, at a dose of 0.25 μg, increased the frequency of penicillin-induced epileptiform activity by producing status epilepticus-like activity, whereas AM-251, at a dose of 0.125 μg, was not effective when applied alone. ACEA, at a dose of 7.5 μg, decreased the frequency of epileptiform activity. Leptin reversed the anticonvulsant activity of ACEA and enhanced the proconvulsant activity of AM-251. This study provides electrophysiological evidence that the proconvulsant activity of leptin is mediated, at least in part, by inhibition of cannabinoids in the experimental model of epilepsy.