title: Modulation of anticonvulsant effects of cannabinoid compounds by GABA-A receptor agonist in acute pentylenetetrazole model of seizure in rat.
abstract: Cannabinoid system plays an important role in controlling neuronal excitability and brain function. On the other hand, modulation of gamma-aminobutyric acid (GABA) transmission is one of the initial strategies for the treatment of seizure. The aim of the present study was to evaluate possible interaction between cannabinoidergic and GABAergic systems in pentylenetetrazole (PTZ)-induced acute seizure in rat. Drugs were administered by intracerebroventricular (i.c.v.) administration 20 min before a single intraperitoneal (i.p.) injection of PTZ and the latency to the first generalized tonic-clonic seizure was measured. Both the cannabinoid receptor agonist WIN55212-2 (10, 30, 50 and 100 μg/rat) and the GABA-A receptor agonist isoguvacine (IGN; 10, 30 and 50 μg/rat) significantly increased the latency of seizure occurrence. Moreover, the fatty acid amide hydrolase inhibitor URB597 showed no anticonvulsive effect while the monoacyl glycerol lipase (MAGL) inhibitor URB602 (10, 50 and 100 μg/rat) protected rats against PTZ-induced seizure. Moreover, co-administration of IGN and cannabinoid compounds attenuated the anticonvulsant action of both WIN55212-2 and IGN in this model of seizure. Our data suggests that exogenous cannabinoid WIN55212-2 and MAGL inhibitor URB602 imply their antiseizure action in part through common brain receptorial system. Moreover, the antagonistic interaction of cannabinoids and IGN in protection against PTZ-induced seizure could suggest the involvement of GABAergic system in their anticonvulsant action.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran. naderi@sbmu.ac.ir
authors.forename: Nima
authors.initials: N
authors.lastname: Naderi
authors.forename: Leila
authors.initials: L
authors.lastname: Ahmad-Molaei
authors.forename: Farzad
authors.initials: F
authors.lastname: Aziz Ahari
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use*; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology; D048588:Benzoxazines / Q000378:metabolism / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism / Q000627:therapeutic use*; D002219:Carbamates / Q000378:metabolism / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000378:metabolism / Q000627:therapeutic use*; D007539:Isonicotinic Acids / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D001549:Benzamides; D048588:Benzoxazines; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D002219:Carbamates; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D007539:Isonicotinic Acids; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C501835:URB602; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D010433:Pentylenetetrazole; C015300:isoguvacine