The role of ¦Á₂-adrenoceptors in the anti-convulsant effects of cannabinoids on pentylenetetrazole-induced seizure threshold in mice

详细信息    查看全文

• 作者：Hamed Shafaroodi ; Leila Moezi ; Arsh Bahrem ; Ahmad Reza Dehpour
• 关键词：Cannabinoid ; ¦Á2-Adrenoceptors ; Pentylenetetrazole ; Seizure ; Mice
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：714
• 期：1-3
• 页码：1-6
• 全文大小：597 K

文摘

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 ¦Á₂-adrenoceptors in different paradigms. Using model of clonic seizure induced by intravenous pentylenetetrazole (PTZ) in male mice, we investigated whether ¦Á₂-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 ¦Á₂ receptor agonist, (1 and 5 mg/kg) showed anticonvulsant effects while yohimbine, a ¦Á₂ 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 ¦Á₂-adrenoceptors could be involved in the anticonvulsant properties of the specific cannabinoid CB₁ agonist ACEA, suggesting that CB₁ cannabinoid and ¦Á₂ receptors have functional interactions in modulation of clonic seizure threshold.