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.
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Authors | Elżbieta Radziszewska, Monika Wolak, Ewa Bojanowska |
Journal | Behavioural pharmacology
(Behav Pharmacol)
Vol. 25
Issue 1
Pg. 53-60
(Feb 2014)
ISSN: 1473-5849 [Electronic] England |
PMID | 24370558
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoxazines
- Dietary Carbohydrates
- Glp1r protein, rat
- Glucagon-Like Peptide-1 Receptor
- Morpholines
- Naphthalenes
- Peptide Fragments
- Peptides
- Piperidines
- Pyrazoles
- Receptor, Cannabinoid, CB1
- Receptors, Glucagon
- Venoms
- AM 251
- exendin (9-39)
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
- Exenatide
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Topics |
- Analysis of Variance
- Animals
- Benzoxazines
(pharmacology)
- Body Weight
(drug effects)
- Dietary Carbohydrates
(pharmacology)
- Drug Interactions
- Exenatide
- Feeding Behavior
(drug effects)
- Glucagon-Like Peptide-1 Receptor
- Male
- Morpholines
(pharmacology)
- Naphthalenes
(pharmacology)
- Peptide Fragments
(pharmacology)
- Peptides
(pharmacology)
- Piperidines
(pharmacology)
- Pyrazoles
(pharmacology)
- Rats
- Rats, Wistar
- Receptor, Cannabinoid, CB1
(agonists, antagonists & inhibitors, metabolism)
- Receptors, Glucagon
(agonists, antagonists & inhibitors, metabolism)
- Venoms
(pharmacology)
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