Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.
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, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/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.
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
Erin M
EM
Rock
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
Nathalie
N
Boulet
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
Cheryl L
CL
Limebeer
Institute of Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel.
Raphael
R
Mechoulam
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada. Electronic address: parkerl@uoguelph.ca.
Linda A
LA
Parker
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D003213:Conditioning, Psychological / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D018021:Lithium Chloride / Q000009:adverse effects*; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000932:Antiemetics; D002186:Cannabinoids; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C402416:HU 308; D018021:Lithium Chloride; C094023:iodopravadoline
AM630; AM630 (PubChem CID: 4302963); Acute nausea; CB(2) receptor; Conditioned gaping; HU-308; HU-308 (PubChem CID: 9844711); Lithium chloride (PubChem CID: 433294); Vomiting