title: Additive effects of cannabinoid CB1 receptors blockade and cholecystokinin on feeding inhibition.
abstract: Cannabinoid CB1 receptor and cholecystokinin-1 (CCK(1)) receptors are located in peripheral nerve terminals of the gut, where they mediate satiety signals. Here we describe a detailed analysis of the interaction of both receptors in the control of feeding of food-deprived rats. Male Wistar rats were deprived for food 24h before testing. Rats were pre-treated with SR141716A (Rimonabant) or WIN 55,212-2 before CCK-8 sulphated administration and tested for food intake 60, 120 and 240 min after last drug injection. In parallel, the effect of Lorglumide--a CCK(1) receptor antagonist--pre-treatment was evaluated on feeding behaviour after SR141716A administration. Results show that SR141716A activates c-Fos expression in brainstem areas receiving vagal inputs. Blockade of CB1 receptors with SR141716A (1 mg/kg) reduces feeding and display additive satiety induction with the CCK(1) receptor agonist CCK-8 sulphated (5, 10, 25 μg/kg). The effect of SR141716A is not blocked by Lorglumide (10 mg/kg), indicating independent sites of action. Conversely, the administration of the CB1 agonist WIN 55,212-2 (2 mg/kg) reduced satiety induced by CCK-8. In conclusion, these results report additive anorectic actions for CCK1 activation and peripheral CB1 receptor blockade providing a framework for combined therapies in the treatment of eating disorders.
authors.affiliation: Departamento de Psicobiología. Facultad de Psicología. Universidad Complutense, Madrid 28223, Spain. lorio@psi.ucm.es
authors.forename: L
authors.initials: L
authors.lastname: Orio
authors.forename: I
authors.initials: I
authors.lastname: Crespo
authors.forename: J A
authors.initials: JA
authors.lastname: López-Moreno
authors.forename: C
authors.initials: C
authors.lastname: Reyes-Cabello
authors.forename: F
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.forename: R
authors.initials: R
authors.lastname: Gómez de Heras
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000503:physiopathology; D048588:Benzoxazines / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D009281:Naphthalenes / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D012844:Sincalide / Q000008:administration & dosage*
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043887:Receptor, Cholecystokinin B; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide; D000077285:Rimonabant