Cholecystokinin and estradiol synergistically potentiate satiety in rats

The ability of octapeptide cholecystokinin (CCK), in interaction with ovarian steroid conditions, to decrease 1-h feeding was studied in 5-h food-deprived Sprague-Dawley rats. In Experiment 1, intact, unilaterally ovariectomized, and bilaterally ovariectomized females and intact males were given IP injections of 0, 0.25, 0.50, and 1.0 microgram/kg b.wt. CCK and were assessed for food ingestion at 1, 3, and 19 h. Food intake at 1 h was suppressed in animals receiving CCK compared to saline (0 dose); the threshold dosage was 1 microgram/kg b.wt. (p < 0.01) in this paradigm. No significant sex difference was observed between the four groups; however, animals with decreased ovarian steroids (intact males and bilaterally ovariectomized females) suppressed ingestion less than animals with greater ovarian steroid levels (intact and unilaterally ovariectomized females) at both the 0.25 and 1.0 microgram/kg b.wt. dosages (p < 0.01). Therefore, in a second experiment, sensitivity to CCK was compared in females in early metestrus, when estrogen levels are decreased, and during late diestrus, when estrogen levels are high, using dosages of 0, 0.25, 1, and 2.5 micrograms/kg b.wt. A statistically significant difference was found between sensitivity at early metestrus and late diestrus at the 2.5 micrograms/kg b.wt. dose only, with food ingestion more reliably depressed during periods of increased estrogen (p < 0.05). These results suggest that estradiol and CCK can have a synergistic effect on satiety.