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: Hamed Shafaroodi, Leila Moezi, Arsh Bahremand, Ahmad Reza Dehpour
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 714 Issue 1-3 Pg. 1-6 (Aug 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23756131 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Arachidonic Acids
• Cannabinoids
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• Receptors, Adrenergic, alpha-2
• arachidonyl-2-chloroethylamide
• Yohimbine
• AM 251
• Clonidine
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants (pharmacology)
• Arachidonic Acids (pharmacology)
• Cannabinoids (pharmacology)
• Clonidine (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Male
• Mice
• Pentylenetetrazole (adverse effects)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Receptor, Cannabinoid, CB1 (agonists, antagonists & inhibitors)
• Receptors, Adrenergic, alpha-2 (metabolism)
• Seizures (chemically induced, physiopathology)
• Yohimbine (pharmacology)