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.
Department of Psychiatry, University of Cincinnati, Cincinnati, OH 45237, USA. duncanea@ucmail.uc.edu
Elizabeth A
EA
Duncan
Gina
G
Davita
Stephen C
SC
Woods
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012528:Satiety Response / Q000187:drug effects*; D012844:Sincalide / Q000008:administration & dosage*; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013997:Time Factors
D013549:Sweetening Agents; D013395:Sucrose; D012844:Sincalide