Differential effects of amphetamine and fenfluramine on dietary self-selection in rats

Daily caloric intakes and dietary self-selection of the three macronutrients, protein, fat and carbohydrate were examined in female rats following administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg, IP) or fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg, IP). Animals were maintained on ground Purina Chow or one of two self-selection regimes, one with a high-caloric fat ration (7.85 kcal/g) and the other with a fat ration isocaloric to the carbohydrate and protein rations (3.76 kcal/g). Animals received drug injections at the beginning of a daily 8-hour feeding period with nutrient intakes measured at 2, 4 and 8 hrs following injections. While both amphetamine and fenfluramine lef to dose-related decreases in total caloric intakes, the two drugs resulted in different temporal patterns of feeding. Amphetamine produced its greatest effect on caloric intake during the first 2 hours of the feeding period, whereas fenfluramine suppressed caloric intake equivalently across the 8-hour feeding period. The two anorectic drugs also led to different patterns of nutrient choice. When animals were given the high-caloric fat ration, amphetamine selectively decreased fat intake while fenfluramine produced decreases in both protein and fat intakes, sparing carbohydrate intake. In contrast, when animals were given the isocaloric fat ration, amphetamine resulted in a general suppression of nutrient intakes while fenfluramine led to a sustained decrease in fat intake with a relative sparing of protein and carbohydrate consumption.