Interaction between urethane and cannabinoid CB1 receptor agonist and antagonist in penicillin-induced epileptiform activity

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.