title: The cannabinoid CB1 antagonists SR 141716A and AM 251 suppress food intake and food-reinforced behavior in a variety of tasks in rats.
abstract: Cannabinoid CB1 receptor agonists, including delta-9-tetrahydrocannabinol (Delta 9-THC) (the main psychoactive ingredient in marijuana) have been shown to increase feeding in rats and humans. Conversely, it has been reported that acute administration of the CB1 receptor antagonist SR 141716A reduces food intake in rats. Based upon this observation, it has been suggested that CB1 antagonists could be useful as appetite suppressant drugs. The present studies were designed to provide a detailed examination of the effects of CB1 antagonists on food intake across a range of paradigms. Two CB1 antagonists (SR 141716A and AM 251) were administered to rats trained on fixed-ratio schedules with two different ratio requirements (fixed-ratio 1 and fixed-ratio 5). Both drugs produced a dose-dependent decrease in lever pressing, and had a relatively long duration of action (T1/2: SR 141716A, 15.1 h; AM 251, 22.0 h). Furthermore, intake of three diets with differing macronutrient composition (lab chow, high fat, high carbohydrate) was studied. Both drugs significantly suppressed intake of all three foods, and there were no significant interactions between drug dose and diet type. These findings support the hypothesis that CB1 receptor antagonists could be useful pharmacological tools for the suppression of appetite.
authors.affiliation: Department of Psychology, University of Connecticut, 406 Babbidge Rd, Storrs, Connecticut 06269, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: K
authors.initials: K
authors.lastname: Winston
authors.forename: L
authors.initials: L
authors.lastname: Swezey
authors.forename: A
authors.initials: A
authors.lastname: Wisniecki
authors.forename: J
authors.initials: J
authors.lastname: Aberman
authors.forename: D J
authors.initials: DJ
authors.lastname: Tardif
authors.forename: A J
authors.initials: AJ
authors.lastname: Betz
authors.forename: K
authors.initials: K
authors.lastname: Ishiwari
authors.forename: A
authors.initials: A
authors.lastname: Makriyannis
authors.forename: J D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D010880:Piperidines; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000502:physiology*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D000077285:Rimonabant
chemical_list: D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011955:Receptors, Drug; D000077285:Rimonabant; D001920:Bradykinin