Evidence for a physiological role for CCK in the regulation of food intake in mice

Abstract

The effects of L-364,718, a cholecystokinin receptor antagonist, on cholecystokinin octapeptide-induced inhibition of food, and its effect on food intake when given alone, were studied in mice using several different feeding paradigms. In all studies, L-364,718 (100 micrograms/kg, 1.0 mg/kg) reversed the ability of cholecystokinin octapeptide to decrease food intake. L-364,718 enhanced food consumption compared with controls in nonfasted mice (100 microgram/kg) and in prefed mice (50, 100, 250 micrograms/kg). The number of reinforcements, using a lever press, was also enhanced by L-364,718 (100 micrograms/kg) compared with control. In other paradigms, L-364,718 failed to enhance food intake. These results are compatible with the suggestion that cholecystokinin may play a physiological role in the regulation of food intake.

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

“…injection of devazepide whereas L-365,260 had no effect. The reversal by the CCK-A receptor antagonist was observed under conditions that did not influence basal food intake as reported previously (18,32). It is also unlikely to represent the anxiolytic-like effect of devazepide because L-365,260, which has established anxiolytic-like properties in mice (43,44), did not influence the food-suppressing effect of leptin-CCK.…”

“…Such a response is unlikely to reflect the anorectic effect of CCK. The peptide was injected at a dose of 3.5 g͞kg, subthreshold to induce a significant decrease in hourly food intake in lean mice, as reported previously (18,19,32). These data provide clear evidence for a synergistic interaction between leptin and CCK leading to short-term reduction in food intake upon a single peripheral injection in lean mice.…”

“…at a subthreshold dose, failed to influence the pattern of leptin-induced change in food intake. Although bombesin is released postprandially and reduces food ingestion in a variety of species including mice, its action is mediated through different mechanisms than CCK, which may account for the difference observed (18,(33)(34)(35).…”

“…Cholecystokinin (CCK) is secreted from small intestinal cells in response to food ingestion and functions as a postprandial satiety signal (13)(14)(15)(16). Numerous studies using CCK receptor agonists and antagonists have extended these findings in several species, including mice and humans (14,(17)(18)(19). Convergent reports indicate that one component of the satiety effect of CCK is initiated at the periphery through the activation of capsaicinsensitive vagal afferent fibers that relays the information to brain sites (20)(21)(22)(23)(24).…”

Orexigenic and anabolic agents

“…Animal studies have shown that CCK antagonists can increase food intake [80]. It would seem worthwhile to examine the effects of CCK antagonists in persons with the anorexia of aging.…”