CB1 antagonism produces behaviors more consistent with satiety than reduced reward value in food-maintained responding in rats

Abstract

Cannabinoid CB1 antagonists are widely known to reduce motivation for food, but it is not known whether they induce satiety or reduce reward value of food. It may therefore be necessary to compare effects of altered satiety and reward food value in the same appetitive task, and determine whether CB1 antagonism produces a behavior pattern similar to either, both, or neither. A fine-grained analysis of fixed-ratio 10 (FR10) responding for palatable food initially included number and duration of, and between, all lever presses and food tray entries in order to differentiate the pattern of suppression of prefeeding from that caused by reducing the reward value of the pellets with quinine. Discriminant function analysis then determined that these manipulations were best differentiated by effects on tray entries, pellet retrieval latencies, and time of the first response. At 0.5 mg/kg, AM 6527 produced similar effects to reducing reward value, but at 1.0 and 4.0 mg/kg, effects were more similar to those when animals were satiated. We conclude that AM 6527 both reduced reward value and enhanced satiety, but as dose increased, effects on satiety became much more prominent. These findings contribute to knowledge about the behavioral processes affected by CB1 antagonism.

Keywords: Cannabinoid; motivation; multivariate analysis; obesity; reward.

Figure 1

FR10 responding for food pellets is suppressed to a similar extent by all three treatments at the low (0.5 mg/kg AM 6527, 4.5 g pellets prefeeding, 0.4 g/kg quinine), medium (1.0 mg/kg AM 6527, 9 g pellets prefeeding, 1.0 g/kg quinine), and high (4.0 mg/kg AM 6527, 18 g pellets prefeeding, 2.0 g/kg quinine) levels. These comparable effects were necessary for interpreting changes in the microstructure of lever pressing. **p < .01 difference from control condition.

Figure 2

Body weights. Vertical lines define the start and end of the six-week test period. Animals were weighed daily, but for clarity, data shown were recorded every Friday during the experiment.

Figure 3

Results of the discriminant function analysis are shown (a) for the overall analysis, collapsed across level, and (b) at each level. Y-axis represents scores resulting from a function composed of five predictors that significantly differentiated prefeeding and quinine conditions. *p < .05, **p < .01. Treatment differences via Tukey’s HSD post hoc analysis. X-axis categories: low = 0.5 mg/kg AM 6527, 4.5 g pellets prefeeding, 0.4 g/kg quinine; medium = 1.0 mg/kg AM 6527, 9 g pellets prefeeding, 1.0 g/kg quinine; high = 4.0 mg/kg AM 6527, 18 g pellets prefeeding, 2.0 g/kg quinine.

Figure 4

When discriminant function analysis was based on AM 6527 in addition to prefeeding and quinine, two functions were identified based on four predictors that contributed significant unique variability. (a) The first function was significant and indicated differences between quinine and both prefeeding and AM 6527, but not between AM 6527 and prefeeding. (b) The second function was not significant. **p < .01. Treatment differences via Tukey’s HSD post hoc analysis. X-axis categories: low = 0.5 mg/kg AM 6527, 4.5 g pellets prefeeding, 0.4 g/kg quinine; medium = 1.0 mg/kg AM 6527, 9 g pellets prefeeding, 1.0 g/kg quinine; high = 4.0 mg/kg AM 6527, 18 g pellets prefeeding, 2.0 g/kg quinine.