• C L Limebeer, E M Rock, R Mechoulam, and L A Parker.
• Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, Ontario, Canada.
• Br. J. Pharmacol. 2012 Nov 1;167(5):1126-36.

Background And PurposeConditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB(1) ) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB(1) receptors.Experimental ApproachWe utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB(1) agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl-induced conditioned gaping and determined if this effect was mediated by CB(1) receptors.Key ResultsCentral, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB(1) agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl-induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB(1) receptors because it was prevented by co-administration of CB(1) antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 µg) administered alone into the VIC did not produce conditioned gaping reactions.Conclusions And ImplicationsThe nausea-relieving effects of CB(1) agonists, but not the nausea-inducing effects of CB(1) inverse agonists, are mediated, at least in part, by their action at the VIC in rats.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

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