Dose-dependent interaction between cholecystokinin and sham feeding

Previous work in this laboratory indicated that decreases in feeding motivation produced by cholecystokinin octapeptide (CCK-8) develop through synergism with signals generated by feeding. In these experiments, we used a runway paradigm to assess the contribution of signals from the oral cavity to this interaction. In contrast to the substantial (44%) impairment in runway performance produced by the combination of 1 microgram/kg CCK-8 and 5 min normal prefeeding, 5 min sham feeding failed to potentiate the effect of 1 microgram/kg CCK-8. Sham feeding in conjunction with this dose of CCK-8 reduced running speed by no more (2%) than CCK-8 alone (9%). Similar results were obtained whether rats were allowed a longer sham feeding interval (12 min) or the prefeeding interval was shifted in time so that it ended only 3 min before the start of the runway test. By contrast, larger doses of CCK-8 interacted with 5 min sham feeding to substantially impair runway performance; significant decreases in speed of 29% and 41% were observed after 2 and 4 micrograms/kg CCK-8, respectively. Results with these doses indicate that synergy between CCK-8 and signals from the oral cavity can contribute to the inhibitory effects of this agent. However, the failure of the combination of the 1 microgram/kg dose and sham feeding to replicate the interaction seen with normal prefeeding indicates the additional involvement of signals arising from food stimulation distal to the oropharynx.