title: Concurrent pharmacological modification of cannabinoid-1 and glucagon-like peptide-1 receptor activity affects feeding behavior and body weight in rats fed a free-choice, high-carbohydrate diet.
abstract: To extend preliminary studies on the effects on food intake of the combined use of cannabinoid (CB) 1 and glucagon-like peptide-1 (GLP-1) receptor agonists and antagonists, the effect of these drugs on the feeding behavior in rats maintained on a free-choice, high-carbohydrate diet was investigated over a longer period of time. Rats were fed a standard diet for 3 days and then fed with both the standard and the high-sucrose chow. After 4 days of the high-calorie diet, the following combination treatments were administered daily by an intraperitoneal injection for the next 3 days: 1 mg/kg AM 251 (a CB1 receptor antagonist) or 1 mg/kg WIN 55,212-2 (a CB1 receptor agonist) together with 3 µg/kg exendin-4 (Ex-4, a GLP-1 receptor agonist) or 160 µg/kg exendin (9-39) [Ex (9-39), a GLP-1 receptor antagonist]. The total daily caloric intake and body weight were significantly reduced in rats treated with Ex-4 and AM 251 or WIN 55,212-2 compared with either of the drugs injected alone and the saline-injected controls. Both drug combinations selectively inhibited ingestion of the high-sucrose chow. Although Ex (9-39) administration did not significantly affect food consumption, it resulted in a marked body weight gain, indicating that the GLP-1 receptor antagonist caused a positive energy balance. It is concluded that AM 251 or WIN 55,212-2 and Ex-4, injected together, exert additive, inhibitory effects on the consumption of high-sugar food.
authors.affiliation: Department of Behavioral Pathophysiology, Medical University of Lodz, Lodz, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Radziszewska
authors.forename: Monika
authors.initials: M
authors.lastname: Wolak
authors.forename: Ewa
authors.initials: E
authors.lastname: Bojanowska
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004347:Drug Interactions; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects*; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology
chemical_list: D048588:Benzoxazines; D004040:Dietary Carbohydrates; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D009025:Morpholines; D009281:Naphthalenes; D010446:Peptide Fragments; D010455:Peptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018027:Receptors, Glucagon; D014688:Venoms; C103505:AM 251; C083773:exendin (9-39); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077270:Exenatide