Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats

The present study investigated the relationship between endogenous CCK and serotonin (5-HT) in fat-induced satiety. Male Wistar rats with duodenal can nulas were adapted to eating 6 h/day along with receiving an infusion of sa line or one of two isocaloric solutions (10 ml, 1 kcal/ml, 0.45 ml/min) var ying in fat and carbohydrate content (20 or 80% energy from fat). Rats were infused 10 min after food presentation. The satiation/satiety response was determined from measures of meal size (MS), intermeal interval (IMI), and total food intake (TFI). Infusion with either fat solution reduced MS compa red with saline; however, the 80% fat infusate reduced TFI and lengthened t he IMI compared with saline and the 20% fat infusate. CCK and 5-HT involvem ent in fat-induced satiety was investigated by preceding the 80% fat infusa te with CCK and/or 5-HT3 receptor antagonists Devazepide (Dev) and Tropiset ron (Trop). A CCK releaser, trypsin inhibitor (TI), was added to the 20% fa t infusate to enhance satiety. Pretreatment with Dev or Trop alone attenuat ed the inhibitory effects of the 80% solution on IMI, whereas reversal of t he inhibitory effects on MS and TFI were sensitive only to Dev at the doses provided. Both antagonists together completely blocked the satiating effec ts of the 80% fat infusate on all feeding variables measured. Addition of T I to the 20% fat infusate lengthened the IMI but did not affect MS or TFI. These results provide evidence for the participation of both endogenous CCK and 5-HT in the satiety response to fat in the intestine.