Effects of glucagon-like peptide-1 receptor stimulation and blockade on food consumption and body weight in rats treated with a cannabinoid CB1 receptor agonist WIN 55,212-2
Elżbieta Radziszewska, Ewa Bojanowska
Med Sci Monit Basic Res 2013; 19:6-11
Background: Glucagon-like peptide-1 (GLP-1) and endocannabinoids are involved in appetite control. Recently we have demonstrated that cannabinoid (CB)1 receptor antagonist and GLP-1 receptor agonist synergistically suppress food intake in the rat. The aim of the present study was to determine the effects of GLP-1 receptor stimulation or blockade on feeding behavior in rats treated with WIN 55,212-2, a CB1 receptor agonist.
Material/Methods: Experiments were performed on adult male Wistar rats. In the first experiment the effects of increasing doses (0.5–4.0 mg/kg) of WIN 55,212-2 injected intraperitoneally on 24-hour food consumption were tested. In further experiments a GLP-1 receptor antagonist, exendin (9-39), and WIN 55,212-2 or a GLP-1 receptor agonist, exendin-4, and WIN 55,212-2 were injected intraperitoneally at subthreshold doses (that alone did not change food intake and body weight) to investigate whether these agents may interact to affect food intake in rats.
Results: WIN 55,212-2 administered at low doses (0.5–2 mg/kg) did not markedly change 24-hour food consumption; however, at the highest dose, daily food intake was inhibited. Combined administration of WIN 55,212-2 and exendin (9-39) did not change the amount of food consumed compared to either the control group or to each agent injected alone. Combined injection of WIN 55,212-2 and exendin-4 at subthreshold doses resulted in a significant decrease in food intake and body weight in rats.
Conclusions: Stimulation of the peripheral CB1 receptor by its agonist WIN 55,212-2 can induce anorexigenic effects or potentiate, even at a subthreshold dose, the effects of exendin-4, a known anorectic agent. Hence, this dual action of the cannabinoid system should be considered in the medical use of CB1 agonists.
Keywords: Rats, Rats, Wistar, Peptides - pharmacology, Peptide Fragments - pharmacology, Naphthalenes - pharmacology, Morpholines - pharmacology, Injections, Intraperitoneal, Feeding Behavior - drug effects, Dose-Response Relationship, Drug, Body Weight - drug effects, Benzoxazines - pharmacology, Animals, Receptor, Cannabinoid, CB1 - metabolism, Receptors, Glucagon - metabolism, Venoms - pharmacology