Clarification of the behavioral functions of peripheral and central cholecystokinin: two separate peptide pools

Cholecystokinin is localized in two distinct systems, the gastrointestinal and the central nervous systems. At both locations, cholecystokinin (CCK) is synthesized, stored, and released, and high affinity binding sites for CCK have been identified. The blood-brain barrier is thought to completely block passage of CCK from the gut to the brain compartment, although CCK can pass from the cerebrospinal fluid out into the blood. A variety of behavioral actions of CCK have been described. Evidence that the actions of CCK on feeding and behavioral sedation are mediated through the peripheral site is reviewed. Recent studies demonstrating behavioral effects of CCK administered in nanogram doses directly into brain nuclei are reviewed. Caveats against administration of microgram doses of CCK into the cerebral ventricles are raised, emphasizing the interpretational difficulties inherent in this approach.