Effects of repeated administration of serotonergic agonists on diet selection and body weight in rats

Food intake, diet selection and body weight gain were examined in three separate experiments in which rats received saline or one of three serotonergic agonists, dexfenfluramine, RU 24969 and fluoxetine. In all experiments, food was available only in the dark period during which time rats were given simultaneous access to two isoenergetic diets which differed in their protein and carbohydrate content. After habituation to this feeding paradigm and intraperitoneal injections, rats were assigned to control or drug group. Saline or a serotonergic agonist was given to the same rat once daily, 15 min prior to feeding, for six consecutive days. All three agonists (1.5 mg/kg for dexfenfluramine and RU 24969; 3 mg/kg for fluoxetine) caused immediate (first two h of feeding) hypophagia which was accounted for by the selective suppression in intake of the high-carbohydrate-low-protein diet. This selective shift in diet choice was sustained upon repeated exposure. Although the effects of these agonists on daily (12-h) feeding was less pronounced, appetite suppression was due entirely to reduced intake of the high-carbohydrate-low-protein diet. Of the three agonists tested, partial tolerance was observed only after dexfenfluramine. Nevertheless, all three agonists caused comparable declines in weight gain. These results suggest that repeated administration of serotonergic agonists has sustained impacts on food intake, diet choice and weight gain.