CCK-octapeptide injected in CSF decreases meal size and daily food intake in sheep

Cholecystokinin octapeptide (CCK-OP) is a potent and specific suppressor of feeding when administered as a continuous lateral cerebral ventricular injection in fasted sheep, and we have proposed that endogenous CCK-OP in the brain is released during meals and acts to terminate feeding. In previous studies, however, only relatively short-term effects of CCK-OP on feeding were examined. In the first experiment of the present series sheep were adapted to a 6-hr feeding period per day. CCK-OP injected continuously for 6 hr into the lateral ventricles reduced feeding during the entire feeding period (809 +/- 72 g, sham; 695 +/- 71 g, carrier; 505 +/- 69 g, CCK-OP; p less than 0.05). In addition mean feed intake for the two days (injection + first post injection day) was significantly reduced by CCK-OP; thus with CCK-OP, sheep did not compensate by the day after injection for the decreased feed intake on injection day. In a second experiment CCK-OP was injected into the lateral ventricles only during four consecutive 15 min meals 2 hours apart. With a dose of 0.159 pmoles/min CCK-OP, size of the second meal was reduced, but with 0.638 pmoles/min CCK-OP feeding during each of the first two meals was reduced and cumulative intake for the four meals was decreased. These results indicate that CCK-OP administered centrally can have long-term effects on feeding, and under appropriate conditions, could result in negative energy balance.