The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin.

1. To determine the role of endogenous cholecystokinin (CCK) in the regulation of food intake, the effects of the potent CCK receptor antagonist L364,718 were investigated on the intake of a palatable diet in non-deprived rats. The effect of a single dose of proglumide was also investigated for comparative purposes. In addition, the ability of L364,718 to antagonize the reduction in food intake produced by exogenous cholecystokinin-octapeptide (CCK8) or bombesin in food-deprived rats was determined. 2. L364,718 (10-100 micrograms kg-1, i.p.) increased the intake of palatable diet during the 30 min test period. Proglumide (300 mg kg-1, i.p.) also increased the intake of palatable diet. Conversely, CCK8 (0.5-5 micrograms kg-1, i.p.) produced a reduction in the intake of the diet. 3. In fasted rats, L364,718 (100 micrograms kg-1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 micrograms kg-1, i.p.) but not that produced by bombesin (50 micrograms kg-1, i.p.). L364,718 did not increase food intake in these animals when measured over a 6 h period. 4. It is concluded that L364,718 is a potent, selective antagonist of the effects of CCK8 on food intake. The observation that L364,718 and proglumide increase the intake of a palatable diet provides some evidence that endogenous CCK is involved in the control of food intake in this model.