Cerebral ventricular injections of CCK-octapeptide and feed intake: The importance of continuous injection

CCK-octapeptide (CCK-OP) is a potent suppressor of feed intake when administered as a continuous injection into the lateral cerebral ventricles of sheep. We compared the effect on feeding of CCK-OP given as bolus and continuous injections to assess the importance of the continuous injection method. A total dose of 30.6 pmoles of CCK-OP given as one, four, or eight bolus injections had no effect on feed intake; whereas the same total dose given as a 45 min continuous injection reduced feed intake 80 percent. We also compared the effects of beginning the continuous injection immediately before, 5 min before, and 15 min before the sheep began a meal. Feed intakes were significantly lower when CCK-OP injection was begun 15 min before the meal, than when injection was begun immediately before or 5 min before the meal, suggesting that the site of action of CCK-OP for its effect on feeding is not the immediate vicinity of the lateral ventricles. The complete lack of effect of bolus injections of CCK-OP is unexpected; the explanation probably awaits further information on kinetics of CSF formation and CCK-OP degradation, site of action of CCK-OP, and the role of the CSF in transport of the peptide.