The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.
OBJECTIVE
Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM-251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a CB1-receptor antagonist, and ACEA (arachidonyl-2-chloroethylamide), a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.


METHODS
In the first set of experiments, 30 min after penicillin injection, AM-251, at doses of 0.125, 0.25, 0.5, and 1 μg, was administered intracerebroventricularly (i.c.v.). In the second set of experiments, 30 min after penicillin injection, ACEA, at doses of 2.5, 5, 7.5, and 15 μg (i.c.v.), was administered. In the third set of experiments, AM-251, at doses of 0.125 and 0.25 μg (i.c.v.), was administered 10 min before ACEA (7.5 μg, i.c.v.) injection.


RESULTS
ACEA, at a dose of 7.5 μg, significantly decreased the frequency of penicillin-induced epileptiform activity without changing the amplitude. ACEA, at doses of 2.5, 5, and 15 μg, had no impact on either frequency or amplitude of epileptiform activity. AM-251, at doses of 0.25 and 0.50 μg, significantly increased the frequency of epileptiform activity. AM-251, at a dose of 0.25 μg (i.c.v.), was the most effective in changing the frequency of penicillin-induced epileptiform activity, and it also caused status epilepticus-like activity. AM-251, at doses of 0.125 and 0.25 μg, 10 min before ACEA (7.5 μg), reversed the anticonvulsant action of ACEA.


CONCLUSIONS
The results of the present study provide electrophysiologic evidence for the role of CB1 receptors in regulating the frequency of epileptiform activity in the model of penicillin-induced epilepsy. To elucidate the precise mechanism of cannabinoid action in the brain during seizure, more advanced electrophysiologic and neurochemical studies are required.
Kozan
Ramazan
R
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, Samsun, Turkey.
Ayyildiz
Mustafa
M
Agar
Erdal
E
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002186:Cannabinoids / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D007276:Injections, Intraventricular; D008297:Male; D010406:Penicillins; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D001095:Arachidonic Acids; D002186:Cannabinoids; D010406:Penicillins; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251