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

Open Access
Publisher Website
Google Scholar
Abstract
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 μg 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 μg kg−1, i.p.) produced a reduction in the intake of the diet. 3 In fasted rats, L364,718 (100 μg kg−1, i.p.) antagonized the reduction in food intake produced by CCK8 (10 μg kg−1, i.p.) but not that produced by bombesin (50 μg 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.