title: Effect of chronic exposure to rimonabant and phytocannabinoids on anxiety-like behavior and saccharin palatability.
abstract: The acute effects of cannabinoid compounds have been investigated in animal models of anxiety-like behavior and palatability processing. However, the chronic effects of cannabinoids in such models are poorly understood. Experiment 1 compared the effects of both acute and chronic (14 days) exposure to the CB(1) receptor inverse agonist/antagonist, rimonabant, and the cannabis-derived CB(1) receptor neutral antagonist, tetrahydrocannabivarin (THCV), on: 1) time spent in the open, lit box in the Light-Dark (LD) immersion model of anxiety-like behavior and 2) saccharin hedonic reactions in the taste reactivity (TR) test of palatability processing. Experiment 2 compared the effects of chronic administration of cannabis-derived Δ(9)-tetrahydrocannabinol (Δ(9)-THC), cannabidiol (CBD) and cannabigerol (CBG) in these models. Tests were administered on Days 1, 7 and 14 of drug administration. In Experiment 1, rimonabant, but not THCV, produced an anxiogenic-like reaction in the LD immersion test and reduced saccharin palatability in the TR test; both of these effects occurred acutely and were not enhanced by chronic exposure. In Experiment 2, Δ(9)-THC also produced an acute anxiogenic-like reaction in the LD immersion test, without enhancement by chronic exposure. However, Δ(9)-THC enhanced saccharin palatability in the TR test on Day 1 of drug exposure only. CBD and CBG did not modify anxiety-like responding, but CBG produced a weak enhancement of saccharin palatability on Day 1 only. The results suggest that the anxiogenic-like reactions and the suppression of hedonic responding produced by rimonabant, are mediated by inverse agonism of the CB(1) receptor and these effects are not enhanced with chronic exposure.
authors.affiliation: Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada N1G 2W1.
authors.forename: Lesley D
authors.initials: LD
authors.lastname: O'Brien
authors.forename: Kiri L
authors.initials: KL
authors.lastname: Wills
authors.forename: Blair
authors.initials: B
authors.lastname: Segsworth
authors.forename: Brittany
authors.initials: B
authors.lastname: Dashney
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004334:Drug Administration Schedule; D054314:Drug Inverse Agonism; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D012439:Saccharin / Q000008:administration & dosage*; D013649:Taste / Q000187:drug effects* / Q000502:physiology*; D055697:Taste Perception / Q000187:drug effects
chemical_list: D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D002185:Cannabidiol; C003403:tetrahydrocannabivarin 9; D013759:Dronabinol; D012439:Saccharin; C037036:cannabigerol; D000077285:Rimonabant