Are peptides truly satiety agents? A method of testing for neurohumoral satiety effects

Because controversy exists as to the interpretation of the known feeding-suppressive effects of various neuropeptides, we attempted to construct a model that could differentiate satiety from other nonspecific effects. Reasoning that a satiety factor should be less inhibiting of feeding in a hungrier animal, whereas aversive agents should be unaffected by hunger, we studied the neuropharmacologic dose responses of five substances administered peripherally to rats at two different degrees of starvation. Included were four neuropeptides with putative satiety effects: cholecystokinin, calcitonin, bombesin and pancreatic polypeptide, as well as the known aversive agent lithium chloride. In the study, cholecystokinin behaved as we postulated a satiety factor would, showing significant effect of starvation at every dose and in the ANOVA. The aversive agent lithium showed overlapping among the starvation groups and no starvation effect by ANOVA. Calcitonin failed to show differences attributable to starvation. Bombesin produced some overlapping of starvation groups and a barely significant starvation effect by ANOVA. Pancreatic polypeptide produced no feeding suppression in the rat. We conclude that cholecystokinin is a short-term satiety signal and that calcitonin acts peripherally by some nonspecific nonsatieting means. Bombesin's effects are unclear but may be nonspecific.