Cannabinoid-1 receptor antagonists reduce caloric intake by decreasing palatable diet selection in a novel dessert protocol in female rats

Abstract

Although many feeding protocols induce obesity, few use multiple foods to analyze diet selection within a single group of animals. To this end, we describe a protocol using time-limited access to a dessert that induces hyperphagia and body weight gain while allowing simple analysis of diet selection. Female retired breeder Sprague-Dawley rats were provided with ad libitum access to standard moist chow (1.67 kcal/g) and daily 8-h nocturnal access to either a sugar gel (SG; 0.31 kcal/g) or sugar fat whip (SFW; 7.35 kcal/g) for 15 days, and food intake and body weight were measured daily. Rats given SFW reduced moist chow intake but not enough to compensate for the large amount of calories consumed from SFW, and thus gained weight. We use this SFW overconsumption protocol to investigate the hypothesis that cannabinoid (CB)1 receptor antagonists reduce caloric intake by selectively decreasing consumption of palatable foods. In two experiments, female retired breeder Sprague-Dawley rats were injected with either Rimonabant (1 mg/kg ip) or vehicle (equal parts polyethylene glycol and saline, 1 ml/kg ip) for 7 days, or one of three doses of AM251 (0.3, 1.0, or 3.0 mg/kg ip), or vehicle for 15 days; food intake and body weight were measured daily. Both Rimonabant and AM251 decreased 24-h caloric intake, but the reduction was specific to a decrease in SFW consumption. This supports the hypothesis that these CB1 receptor antagonists impact feeding by modulating the perception of palatability.

Fig. 1.

Means ± SE daily caloric intake of rats given ad libitum access to moist chow and 8 h/day access to either sugar gel (SG; n = 8), sugar fat whip (SFW; n = 8), or no additional diet (n = 8). A: total caloric intake. B: caloric intake from moist chow. C: caloric intake from dessert. The horizontal dotted line is the mean baseline consumption of moist chow only of all the rats before experimental manipulations and is shown for comparison. Rats given SFW consumed significantly (P < 0.05) more total calories than the other groups on days 1–10 and significantly fewer calories from chow than the other groups on all days. Rats given SG consumed fewer calories from moist chow than rats given no dessert on days 7–15. Rats given SFW consumed significantly more calories from SFW than rats given SG consumed from SG on all days.

Fig. 2.

Means ± SE daily change in body weight from baseline in rats fed the desserts described in Fig. 1. The vertical dotted line represents when the rats were taken off study and returned to access to moist chow only. Rats given SFW gained significantly more weight than rats given no dessert or rats given SG. Rats given SFW gained weight every day and weighed more than rats given no dessert or given SG on all days. Rats given no dessert and rats given SG did not significantly change in body weight from baseline.

Fig. 3.

Means ± SE daily caloric intake of rats injected with either vehicle (n = 12) or cannabinoid (CB) receptor (CB1R) antagonist Rimonabant (n = 12) while given ad libitum access to moist chow and 8 h access to SFW. A: total caloric intake. B: caloric intake from moist chow. C: caloric intake from SFW. The horizontal dotted line represents the mean baseline consumption of moist chow only of all the rats prior to experimental manipulations and is shown for comparison. Rats injected with Rimonabant consumed significantly fewer total calories than rats injected with vehicle on days 1–5. Rats injected with Rimonabant consumed an equivalent number of calories from moist chow as rats injected with vehicle on all days, and both groups consumed less chow than during baseline. Rats injected with Rimonabant consumed significantly fewer calories from SFW than rats injected with vehicle on days 1–5.

Fig. 4.

Means ± SE daily change in body weight from baseline in rats on the drug regimen and dessert protocol described in Fig. 3. Rats injected with Rimonabant while given SFW gained significantly less weight than rats injected with vehicle while given SFW. Rats injected with Rimonabant while given SFW weighed less than those injected with vehicle while given SFW on every day except day 2, and maintained a negative body weight change until day 5.

Fig. 5.

Means ± SE daily caloric intake of rats injected with either vehicle (n = 6) or 1 of 3 doses of CB1 receptor antagonist AM251 (each, n = 6) while on the dessert protocol described in Fig. 3. A: total caloric intake. B: caloric intake from moist chow. C: caloric intake from dessert. The horizontal dotted line represents the mean baseline consumption of moist chow only of all the rats prior to experimental manipulations and is shown for comparison. Rats injected with 3.0 mg/kg AM251 consumed significantly fewer total calories than rats injected with vehicle on days 1–8. Rats injected with 3.0 mg/kg AM251 consumed significantly fewer total calories than rats injected with 0.3 mg/kg AM251 on days 4 and 5. Rats injected with 0.3 and 3.0 mg/kg AM251 consumed an equivalent number of calories from moist chow as rats injected with vehicle on all days. Rats injected with 1.0 mg/kg AM251 consumed significantly fewer calories from chow than rats in the other groups on days 7, 8, 10, and 12. Rats injected with 3.0 mg/kg AM251 consumed significantly fewer calories from SFW than rats injected with vehicle on days 1–3 and 5–8.

Fig. 6.

Means ± SE daily change in body weight from baseline in rats on the drug regimen and dessert protocol described in Fig. 5. Rats injected with any dose of AM251 gained less weight than rats injected with vehicle on days 6–15. Rats injected with 3.0 mg/kg AM251 gained less weight than rats injected with 0.3 or 1.0 mg/kg AM251 on days 1–8. Rats injected with 3.0 mg/kg while given SFW weighed less than those injected with vehicle while given SFW on every day and maintained a negative body weight change until day 8.