DEVAZEPIDE ALTERS MEAL PATTERNS IN LEAN, BUT NOT OBESE, MALE ZUCKER RATS

Meal patterns were recorded for 10.5 h in six lean and eight obese adult male Zucker rats after treatment with the cholecystokinin type A (CCK,) receptor antagonist, devazepide (750 mu g/kg, IP, at 1330 h) or vehicle. In lean rats, devazepide significantly increased total food intake by 11%, average meal size by 35%, and meal duration by 49%. Devazepide also significantly decreased the average number of meals by 18%, although this was a smaller effect. Devazepide had none of these effects in obese rats. Devazepide treatment altered the meal pattern of lean rats so that it was similar to that of obese rats. These results demonstrate that endogenous CCK has a satiating effect in lean, but not in obese, male Zucker rats, which is the first demonstration of a loss of a physiological satiety signal in the obese Zucker rat. This defect could be due to: 1) a decrease in the release of endogenous CCK, 2) a decrease in the rate of CCK synthesis, or 3) the production of an abnormal form of CCK.