Systemic administration of cholecystokinin (CCK) inhibits operant water intake in rats: implications for the CCK-satiety hypothesis.

The demonstration that intraperitoneal administration of the sulphated octapeptide of cholecystokinin (CCK-8S) inhibits food but not water intake in rats, has led to the hypothesis that endogenous peripheral CCK acts as a food-specific satiety factor. As water-deprived rats given free access to water can satisfy their thirst fairly rapidly, it is conceivable that the apparent lack of effect of CCK on water intake reported previously may have been because the animals had satisfied their thirst before the full effects of the peptide had become apparent. To test this possibility, the effects of intraperitoneal (i.p.) administration of CCK-8S, at doses that had previously been shown to inhibit food intake, were investigated on water intake in rats trained to make operant responses for water reinforcements. Such a paradigm has the merit of slowing down the rate at which a water-deprived rat can quench its thirst, thus extending the period over which the effects of CCK-8S on water intake may be assessed. CCK-8S (2, 4 or 8 micrograms kg-1, i.p.) produced a dose-related suppression of operant water intake in 16 h water-deprived rats during the first 30 min after administration. Additional experiments indicated that, as with feeding, CCK-8S inhibits water intake by an action at peripheral CCKA receptors. These finding have important implications for the CCK-satiety hypothesis as they show that the effect of the peptide on ingestive behaviours in the rats is not specific for food intake and suggest that it is unlikely that CCK is a mediator of satiety.