Central nervous system cholecystokinin and the control of feeding behavior in sheep

There is increasing evidence that brain cholecystokinin (CCK) peptides function as neuropeptide signals of satiety. Injection of as little as femtomole amounts of CCK-8 into the cerebral ventricles selectively decreased feeding in sheep, and other species (chicken, pig, hamster and rat) also decrease feeding in response to CNS injections of CCK. As would be expected with a physiological satiety agent, CCK-8-induced suppression of feeding interacts in a corrective manner with the energy deficit of the animal, in that the longer the fasting period, the greater the amount of CCK-8 required to suppress feeding. Although it has not been possible to measure changes in concentration of CCK in cerebrospinal fluid (CSF) with feeding, neutralization of endogenous CCK by administration of CCK antisera into the CSF delayed satiety in sheep. This and other evidence not only supports a physiological role for endogenous brain CCK in feeding behavior, but also suggest that CSF transports CCK to site(s) of action. Little is known of CCK's mechanisms of action, but because CNS CCK also causes changes in both gut motility and secretion of insulin and glucagon, the satiety could result directly from effects on behavior, and indirectly through metabolic changes. Evidence of selective uptake of CCK from CSF suggested involvement of hypothalamic periventricular areas in these functions. Recent findings in sheep of a 60% decrease in CCK content in anterior hypothalamus two hrs after a meal also supports this hypothesis.