title: Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2.
abstract: Cannabinoid and PPAR receptors show well established interactions in a set of physiological effects. Regarding the seizure-modulating properties of both classes of receptors, the present study aimed to evaluate the roles of the PPAR-gamma, PPAR-alpha and CB1 receptors on the anticonvulsant effects of WIN 55,212-2 (WIN, a non selective cannabinoid agonist). The clonic seizure thresholds after intravenous administration of pentylenetetrazole (PTZ) were assessed in mice weighing 23-30 g. WIN increased the seizure threshold dose dependently. Pretreatment with pioglitazone, as a PPARγ agonist, potentiated the anticonvulsant effects of WIN, while PPARγ antagonist inhibited these anticonvulsant effects partially. On the other hand PPARα antagonist reduced the anticonvulsant effects of WIN significantly. Finally the combination of CB1 antagonist and PPARα antagonist could completely block the anticonvulsant properties of WIN. Taken together, these results show for the first time that a functional interaction exists between cannabinoid and PPAR receptors in the modulation of seizure susceptibility.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Ebrahimi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ramtin
authors.initials: R
authors.lastname: Gholizadeh
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: rahimian78@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Bardia
authors.initials: B
authors.lastname: Varastehmoradi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maziar
authors.initials: M
authors.lastname: Gooshe
authors.affiliation: Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein Nayeb
authors.initials: HN
authors.lastname: Aghaei
authors.affiliation: Physiology Research Center and Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: mousavik@gmail.com.
authors.forename: Kazem
authors.initials: K
authors.lastname: Mousavizadeh
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010080:Oxazoles / Q000494:pharmacology; D010433:Pentylenetetrazole; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors*; D000077205:Pioglitazone; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D012640:Seizures / Q000188:drug therapy*; D045162:Thiazolidinediones / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000927:Anticonvulsants; D048588:Benzoxazines; D063387:Cannabinoid Receptor Antagonists; C449302:GW 6471; D009025:Morpholines; D009281:Naphthalenes; D010080:Oxazoles; D047492:Peroxisome Proliferator-Activated Receptors; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D045162:Thiazolidinediones; C103505:AM 251; D014443:Tyrosine; 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; D000077205:Pioglitazone
keywords: Cannabinoid; PPAR-alpha; PPAR-gamma; Seizure; WIN 55,212-2 mesylate