Changes in the satiating effect of cholecystokinin over repeated trials

The study investigated the reasons for discrepant published results concerning a diminution of the satiating action of cholecystokinin (CCK) when it is administered over several trials. Throughout the experiment, rats were maintained on a schedule in which they were fasted for 5.5 h (except 5 ml of milk), and then given access to a 10% sucrose solution for 30 min. Following a baseline period, rats received 6 mug/kg CCK-8 every day (consecutive group) or every third day (intermittent group), or saline (saline group), 15 min prior to the sucrose. In the consecutive group, CCK-8 significantly reduced meal size on day 1 (85.1+/-7.4% of baseline) compared to the saline group (106.9+/-7.5% of baseline), p<0.05. This reduction was eliminated by day 5 (consecutive group=94.9+/-4.7% of baseline, saline group=98.0+/-5.2% of baseline). In contrast, the intermittent group never became insensitive to the effect of CCK-8, reducing their intake comparably after the tenth (intermittent group=138.7+/-8.2% of baseline, saline group=176.0+/-9.1% of baseline, p<0.01), and first CCK-8 injection (intermittent group=77.0+/-6.1% of baseline, saline group=106.9+/-7.5% of baseline, p<0.01). Although it has been hypothesized that this phenomenon is due to behavioral tolerance, the results of this experiment suggest an alternate hypothesis; i.e., that the diminution of the effect of CCK-8 over consecutive administrations is due to the extinction of a previously learned response to endogenous CCK.