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Am J Physiol Regul Integr Comp Physiol 277: R802-R811, 1999;
0363-6119/99 $5.00
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Vol. 277, Issue 3, R802-R811, September 1999

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

Brenda K. Smith1, David A. York1,2, and George A. Bray1,2

1 Obesity, Diabetes and Metabolism Section, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808; and 2 Department of Physiology, Louisiana State University School of Medicine, New Orleans, Louisiana 70112

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-HT1B/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.

paraventricular nucleus; fenfluramine; quipazine; food intake; preference; 5-hydroxytryptamine


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