Cannabinoid 2 (CB₂) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats

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• 作者：Erin M. Rock^a ; Nathalie Boulet^a ; Cheryl L. Limebeer^a ; Raphael Mechoulam^b ; Linda A. Parker^a ; ^{parkerl@uoguelph.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HU-308 (PubChem CID ; 9844711) ; AM630 (PubChem CID ; 4302963) ; Lithium chloride (PubChem CID ; 433294)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 September 2016
• 年：2016
• 卷：786
• 期：Complete
• 页码：94-99
• 全文大小：517 K

文摘

We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB₂) receptor. We investigated the effect of the selective CB₂ agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB₂ receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5 mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5 mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB₂ receptor agonist to reduce nausea in animal models, indicating that targeting the CB₂ receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting.