title: Intra-visceral insular cortex 2-arachidonoylglycerol, but not N-arachidonoylethanolamide, suppresses acute nausea-induced conditioned gaping in rats.
abstract: The visceral insular cortex (VIC) has previously been shown to play a critical role during acute nausea-induced conditioned gaping in rats. Specifically, localized administration of the conventional anti-emetic, ondansetron or the synthetic cannabinoid, HU210, interferes with the establishment of conditioned gaping, likely by reducing the effects of an illness-inducing treatment. However the precise role of the VIC in endocannabinoid-suppression of nausea remains unknown; thus we investigated the potential of localized intra-VIC endocannabinoid administration to interfere with acute nausea-induced conditioned gaping behavior in male Sprague-Dawley rats. Animals received an intraoral infusion of saccharin (0.1%) followed by intra-VIC exogenous N-arachidonoylethanolamide (AEA; 0.4, 4 μg) or 2-arachidonoylglycerol (2-AG; 0.5, 1 μg), and were subsequently injected with nausea-inducing LiCl (0.15M) 15 min later. Bilateral intra-VIC infusions of 2-AG (1 μg, but not 0.5 μg) dose-dependently suppressed conditioned gaping, whereas exogenous AEA was without effect. Interestingly, 2-AG reduced conditioned gaping despite additional pretreatment with the selective cannabinoid receptor type 1 (CB1) antagonist, AM-251; however, concomitant pretreatment with the cyclooxygenase inhibitor, indomethacin (0.5 μg), blocked the suppressive effects of intra-VIC 2-AG. These findings suggest that the modulatory role of the endocannabinoid system during nausea is driven largely by the endocannabinoid, 2-AG, and that its anti-nausea effects may be partly independent of CB1-receptor signaling through metabolic products of the endocannabinoid system.
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Sticht
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Limebeer
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
authors.forename: B R
authors.initials: BR
authors.lastname: Rafla
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada. Electronic address: parkerl@uoguelph.ca.
authors.forename: L A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology*; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000932:Antiemetics; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; D018021:Lithium Chloride; C078814:anandamide
keywords: 2-arachidonoylglycerol; anandamide; endocannabinoid; gape; rat; visceral insular cortex