ABSTRACT
Previous experimental studies have shown that various anesthetics alter the effects of cannabinoid agonists and antagonists on the cardiac response to different stimuli. Since no data have shown an interaction between urethane and cannabinoid signaling in epilepsy, we examined the suitability of urethane with regard to testing the effects of a cannabinoid CB1 receptor agonist and an antagonist on penicillin-induced epileptiform activity in rats. Permanent screw electrodes for electrocorticographic (ECoG) recordings, and a permanent cannula for administration of the substances to the brain ventricles, were placed into the cranium of rats. Epileptiform activity was induced by injection of penicillin through the cannula in conscious animal. The CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA; 7.5 µg) and the CB1 receptor antagonist [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide] (AM-251; 0.25 µg) were administered intracerebroventricularly 30 minutes after the penicillin application in urethane-anesthetized and conscious animals. Urethane completely eliminated spontaneous ictal events in ECoG recordings and reduced the frequency and total amount of epileptiform activity. It did not alter either the proconvulsant effects of AM-251 or the anticonvulsant effects of ACEA on penicillin-induced epileptiform activity. The electrophysiological evidence suggests that there is no possible interaction between urethane and cannabinoid CB1 receptors in this experimental model of epilepsy.
Subject(s)
Anticonvulsants/pharmacology , Cannabinoid Receptor Agonists/pharmacology , Penicillins/pharmacology , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Urethane/pharmacology , Animals , Epilepsy/chemically induced , Male , Rats, WistarABSTRACT
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
