BLOCKADE OF TYPE-A, BUT NOT TYPE-B, CCK RECEPTORS POSTPONES SATIETY IN RHESUS-MONKEYS

The exogenous administration of the brain/gut peptide cholecystokinin (CCK) inhibits food intake in a variety of species, including subhuman primates and humans. To determine the role of endogenously released C CK in the control of food intake in rhesus monkeys, we examined the ab ility of the selective type A and type B CCK antagonists devazepide an d L-365260 to affect total daily food intake and various meal patterns . Various doses of the antagonists were administered intragastrically 30 min before a daily 4-h feeding period. One-gram food pellets were d elivered in response to lever pulls, and intake was computer monitored . Intragastric administration of the type A CCK receptor antagonist de vazepide (10-320 mug/kg) significantly increased food intake in a dose -related fashion. The threshold for increasing intake was 32 mug/kg, a nd a maximal effect was obtained at a dose of 100 mug/kg that increase d total 4-h food intake by 47%. The effect of devazepide on food intak e was mediated by significant increases in the size and duration of th e initial meal, lengthening of the subsequent intermeal interval, and a decrease in the satiety ratio (intermeal interval/lst meal size). In contrast, intragastric administration of the type B CCK receptor anta gonist L-365260 (3.2-320 mug/kg) did not significantly affect total fo od intake or any of the meal parameters. These data demonstrate that e ndogenously released CCK acting through type A CCK receptors plays a r ole in regulating food intake in rhesus monkeys.