Selective effects of CGS 10686B, dl-fenfluramine or fluoxetine on nutrient selection

We compared the effects of CGS 10686B (a new drug that blocks serotonin reuptake), on nutrient selection and total food consumption with those of two other serotoninergic drugs, dl-fenfluramine and fluoxetine. The animals were given simultaneous free access to two isocaloric 40%-carbohydrate diets in separate food pans; one of these diets (5% protein) was shown to enhance brain serotonin synthesis by raising brain tryptophan levels; the other (45% protein) did not. CGS 10686B (4-7.5 mg/kg) markedly decreased (60-70%) consumption of the 5% protein diet, with a smaller effect (20-30%) on consumption of the 45% protein diet. Hence, it increased the ratio of protein to carbohydrate in the total food consumed. Higher doses (12.5-15 mg/kg) were no longer nutritionally-specific. Fluoxetine, which also blocks serotonin reuptake, and dl-fenfluramine, which both releases serotonin and suppresses its reuptake, had similar effects on nutrient intake; dl-fenfluramine was most potent and fluoxetine least. None of the drugs selectively affected carbohydrate or protein intake if the composition of the test diets provided was such that neither diet, eaten alone, would increase brain serotonin. These observations affirm that drugs which enhance serotoninergic neurotransmission selectively suppress the intake of high-carbohydrate, low-protein meals which increase brain serotonin synthesis.