Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate

Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-h ydroxytryptamine, 5-HT) recently was shown to suppress fat and occasionally protein but not carbohydrate intake in rats when a macronutrient selection paradigm was employed. These reports contrast with the prevailing literatu re, which for the past decade has described a role for serotonin neurotrans mission in the modification of dietary carbohydrate consumption. To test th e hypothesis that the suppression of fat selection and/or consumption by sy stemic serotonin agonists involves stimulation of central 5-HT receptors, a series of experiments was performed in nondeprived rats. In experiment 1, third cerebroventricular (3V) infusion of the nonselective 5-HT antagonist metergoline prevented the reduction in fat but not carbohydrate feeding cau sed by systemic dF Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT1B/2C receptor agonists D-norfen fluramine (DNF) or quipazine inhibited fat intake exclusively. Next, the in fusion of DNF or 5-HT into the region of the paraventricular nucleus (PVN) reduced both fat and protein intake (experiments 4 and 5). Finally, in expe riment 6, when rats were grouped by baseline diet preference, 5-HT infused into the PVN led to a dose-related decrease in fat intake in both carbohydr ate- and fat-preferring rats. In contrast, there were no dose effects of 5- HT on carbohydrate or protein intake in either preference group. However, i n fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exoge nous serotonergic drugs in the hypothalamus to reduce fat rather than carbo hydrate intake and suggest that higher baseline fat intake enhances respons ivity to serotonergic drugs.