Chronic intraventricular administration of cholecystokinin octapeptide (CCK-8) suppresses feeding in rats

Cholecystokinin octapeptide (CCK-8) is known to suppress feeding in sheep, pigs, golden hamsters and rats following acute intracerebriventricular (i.c.v.) injection. In this study, we report the effects of chronically administered i.c.v. CCK-8 on long-term food intake in rats. After baseline food intake was established over a period of 3 days, rats were implanted with Alzet osmotic minipumps, which delivered 1.0 μl/h. Three groups of animals were prepared which received saline (vehicle) or CCK-8 at 12.25 μg/day (low dose) or CCK-8 at 122.5 μg/day (high dose). Surgical preparation of the animals with the intraventricular cannula and the osmotic minipump resulted in an initial reduction in food consumption in all groups. In the saline group daily food consumption returned to presurgery values by day 4. Similar results were observed with the low dose of CCK-8. In contrast, in animals receiving the high concentrations of CCK-8, the initial fall in feeding was more prominent and though it rose during the 7-day infusion interval, it remained statistically below control during this period. After termination of the infusion, daily food consumption rose to normal levels during the next 3 days. For comparison, the cumulative difference between daily food consumption over the period of 8 days during infusion and pre-infusion control was 39.9 ± 10.0 g/24 h in the saline group. In CCK-8-infused animals, food consumption after pump implantation was reduced by an integrated value of 35.5 ± 5.0 g/24 h at low dose and 117.4 ± 20.2 g/24 h at high dose. Thus, by all indices, i.c.v. infusion of CCK-8 at high dose, but not at low dose resulted in a significant reduction of food intake as compared ti saline (P < 0.05). Water intake was not not altered by the infusion of CCK-8 at low or high dose vs saline.