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

• Published in: The American journal of physiology Vol. 277; no. 3; pp. R802 - R811
• Main Authors: Smith, B.K, York, D.A, Bray, G.A
• Format: Journal Article
• Language: English
• Published: United States 01-09-1999
• Subjects: Animals; dietary carbohydrate; Dietary Carbohydrates - administration & dosage; Dietary Carbohydrates - metabolism; Dietary Fats - administration & dosage; Dietary Fats - metabolism; dietary protein; Dietary Proteins - administration & dosage; Dietary Proteins - metabolism; food choices; hypothalamus; Hypothalamus - physiology; Male; paraventricular nucleus; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - physiology; Serotonin - physiology; Signal Transduction
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpregu.1999.277.3.R802

Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-hydroxytryptamine, 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 literature, which for the past decade has described a role for serotonin neurotransmission in the modification of dietary carbohydrate consumption. To test the hypothesis that the suppression of fat selection and/or consumption by systemic 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 caused by systemic dF. Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT(1B/2C) receptor agonists D-norfenfluramine (DNF) or quipazine inhibited fat intake exclusively. Next, the infusion 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 experiment 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 carbohydrate- and fat-preferring rats. In contrast, there were no dose effects of 5-HT on carbohydrate or protein intake in either preference group. However, in fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exogenous serotonergic drugs in the hypothalamus to reduce fat rather than carbohydrate intake and suggest that higher baseline fat intake enhances responsivity to serotonergic drugs.