title: The role of α₂-adrenoceptors in the anti-convulsant effects of cannabinoids on pentylenetetrazole-induced seizure threshold in mice.
abstract: Cannabinoid system plays a pivotal role in the seizure threshold modulation which is mainly mediated through activation of the cannabinoid CB₁ receptor. There is also several evidence of interaction between cannabinoid system and α₂-adrenoceptors in different paradigms. Using model of clonic seizure induced by intravenous pentylenetetrazole (PTZ) in male mice, we investigated whether α₂-adrenoceptors is involved in the effects of cannabinoids on the seizure threshold. Injection of the selective cannabinoid CB₁ agonist ACEA (2 mg/kg) significantly (P<0.01) increased the seizure threshold which was prevented by pretreatment with the selective CB1 antagonist AM251 (1 mg/kg, i.p.). The highest doses of clonidine, a α₂ receptor agonist, (1 and 5 mg/kg) showed anticonvulsant effects while yohimbine, a α₂ receptor antagonist, (0.01, 0.1, 1, and 10 mg/kg) did not induce any significant effect on PTZ seizure threshold. Pretreatment with clonidine (0.1 and 0.5 mg/kg) significantly reversed the anticonvulsant effect of ACEA (2 mg/kg). Yohimbine (0.1, 1, and 10 mg/kg) pretreatment of mice enhanced the clonic seizure threshold of ACEA (1 mg/kg), significantly. Combination of non-effective doses of AM251 (0.1 mg/kg) and clonidine (0.01 mg/kg) showed additive effect in blocking the anticonvulsant effect of ACEA (2 mg/kg). In conclusion, our findings demonstrated that α₂-adrenoceptors could be involved in the anticonvulsant properties of the specific cannabinoid CB₁ agonist ACEA, suggesting that CB₁ cannabinoid and α₂ receptors have functional interactions in modulation of clonic seizure threshold.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Arsh
authors.initials: A
authors.lastname: Bahremand
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000009:adverse effects*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D001095:Arachidonic Acids; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018341:Receptors, Adrenergic, alpha-2; C119325:arachidonyl-2-chloroethylamide; D015016:Yohimbine; C103505:AM 251; D003000:Clonidine; D010433:Pentylenetetrazole
keywords: Cannabinoid; Mice; Pentylenetetrazole; Seizure; α(2)-Adrenoceptors