title: The interaction between ghrelin and cannabinoid systems in penicillin-induced epileptiform activity in rats.
abstract: 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 CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) (2.5 and 7.5 µg), 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 and 0.5 µg) and ghrelin (0.5 and 1 µg) 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 µg, i.c.v.) or a non-effective dose of ACEA (2.5 µg, i.c.v.) or effective doses of AM-251 (0.25, 0.5 µg, i.c.v.) 10 minutes after ghrelin application. A 1 µg dose of ghrelin suppressed penicillin-induced epileptiform activity. The administration of a 0.25 µg dose of AM-251 increased the frequency of penicillin-induced epileptiform activity by producing status epilepticus-like activity. A 7.5 µg dose of ACEA decreased the frequency of epileptiform activity, whereas a non-effective dose of ACEA (2.5 µg) did not change it. Effective doses of AM-251 (0.25, 0.5 µg) reversed the ghrelin's anticonvulsant activity. The application of non-effective doses of ACEA (2.5 µg) together with ghrelin (0.5 µg) within 10 minutes caused anticonvulsant activity, which was reversed by the administration of AM-251 (0.25 µg). The electrophysiological evidence from this study suggests a possible interaction between ghrelin and cannabinoid CB1 receptors in the experimental model of epilepsy.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Arslan
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ayyildiz
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey. Electronic address: eragar@omu.edu.tr.
authors.forename: Erdal
authors.initials: E
authors.lastname: Agar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D054439:Ghrelin / Q000008:administration & dosage / Q000502:physiology*; D057967:Infusions, Intraventricular; D008297:Male; D010406:Penicillins; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D054439:Ghrelin; D010406:Penicillins; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251
keywords: Cannabinoids; Epilepsy; Epileptiform activity; Ghrelin; Penicillin