title: The role of CB1-receptors in the proconvulsant effect of leptin on penicillin-induced epileptiform activity in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Arslan
authors.forename: Sabiha Kubra
authors.initials: SK
authors.lastname: Alici
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ayyildiz
authors.forename: Erdal
authors.initials: E
authors.lastname: Agar
mesh_terms: D000818:Animals; D003292:Convulsants / Q000008:administration & dosage* / Q000633:toxicity; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D057967:Infusions, Intraventricular; D020738:Leptin / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D010406:Penicillins / Q000008:administration & dosage* / Q000633:toxicity; D010880:Piperidines / Q000008:administration & dosage / Q000633:toxicity; D011720:Pyrazoles / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D003292:Convulsants; D020738:Leptin; D010406:Penicillins; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251