Modification of daily food intake induced by concurrent changes in glucagon-like peptide-1 (GLP-1) and cannabinoid CB1 receptor activity in the rat
Feeding behavior is closely related to the circadian activity of humans and animals. The endocannabinoid system is known to affect the circadian changes in energy balance and gastrointestinal peptides were found to change the expression of CB1 receptor in vagal terminals in the alimentary tract. Therefore, we have examined whether the anorectic action of CB1 receptor antagonist, AM 251, may be modified by activation or blockade of GLP-1 receptor. Male Wistar rats were housed in individual cages and maintained on a 12:12 hour light-dark cycle with free access to standard, pelleted rat chow and water. Each rat received a preweighed amount of food every day throughout the experiment. The animals were injected intraperitoneally either with a CB1 receptor antagonist, AM251 (2 mg/kg bw.), followed 15 min later by a GLP-1 antagonist, exendin (9-39) (160 µg/kg bw.), or AM 251 (1 mg/kg bw.) followed 15 min later by a GLP-1 agonist, exendin 4 (1.5 µg/kg bw.). All injections were made 1 – 1.5 hour before lights off. 24-hour food intake was recorded two days before and two days after the injection. AM 251 at a dose of 2 mg/kg significantly reduced daily food intake and concomitant injection of exendin (9-39), at a dose found previously to prevent the action of other anorectic agents, had no effect on a AM 251-induced decrease in food consumption. On the other hand, either 1 mg/kg AM 251 or 1.5 µg exendin-4 administered alone had no significant effect on 24-hour food intake. When, however, these drugs were co-injected, a marked reduction in 24-hour food intake occurred. These results indicate that (1) the anorectic action of CB1 receptor antagonist is not mediated by GLP-1 and (2) the CB1 receptor antagonist and GLP-1 receptor agonist act synergistically to reduce the daily food consumption in the rat when injected before of the nocturnal feeding phase. This work was supported by the National Centre for Science (grant No. 0056/B/ P01/2011/40).
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