Both the endocannabinoids and glucagon-like peptide-1 (GLP-1) are known to control intake of highly palatable food. We have investigated whether WIN 55,212-2 (a cannabinoid receptor 1 agonist) and exendin-4 (Ex-4, a GLP-1 agonist) may interact to change feeding behavior in rats maintained on a free-choice, high-sucrose diet. The rats were presented with both their regular and highsucrose chow throughout the experiment. After 4 days, they were injected once daily for 3 days with either 1 mg/kg WIN 55,212-2, 3 µg/kg Ex-4 or both. Ex-4 and, unexpectedly, WIN 55,212-2 injected separately diminished the mean daily caloric intake. When both drugs were administered together, the daily caloric intake was further reduced, the consumption of high-sugar chow was almost completely inhibited but the intake of standard diet was increased and was significantly higher than that in either Ex-4-, WIN 55- 212-2- or saline-injected rats. These changes were associated with a marked reduction in body weight in both WIN-55,212-2- and Ex-4+WIN-55,212-2-treated animals wherein the difference between these groups was not significant. In conclusion, subchronic treatment with WIN 55-212-2 resulted in the reduced total caloric intake and Ex-4 enhanced this effect. Moreover, combined administration of WIN 55-212-2 and Ex-4 reversed food preferences (i.e., decreased sweet chow and increased standard chow consumption).
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