Medial hypothalamic serotonin: role in circadian patterns of feeding and macronutrient selection

Abstract

Hypothalamic serotonin (5-HT) is believed to have an inhibitory effect on food intake in a variety of species. To define more precisely the nature of this effect, this study investigated the effects of medial hypothalamic 5-Ht injection on natural patterns of macronutrient intake in freely feeding rats. Serotonin (5–20 nmol) was injected directly into the paraventricular nucleus (PVN) of brain-cannulated rats maintained ad libitum on pure macronutrient diets, protein, carbohydrate and fat, and measurements of nutrient intake were taken one hour later. To assess whether the action of 5-HT on macronutrient intake varies across the light-dark cycle, these tests were conducted at 3 different times in the nocturnal feeding period, during hours 1, 6 and 11 after lights out. The results demonstrate that the suppressive effect of PVN 5-HT on food intake is dose dependent, nutrient selective, as well as time dependent. Specifically, PVN injection of 5-HT, at all doses tested, was effective at only one time of the nocturnal cycle, namely, at the onset of the active, dark period. While no behavioral effect of 5-HT was detected in the middle and late phases of the dark, a strong, dose-dependent reduction of nutrient intake was revealed immediately after lights out. This suppressive effect was characterized by a highly selective decrease in carbohydrate intake, along with a significant enhancement in preference for protein, as well as for fat, and little change in total caloric intake. While the rat's nutrient preferences also varied across the nocturnal cycle, the selective effects of 5-HT on nutrient intake occurred independently of these shifts in baseline eating patterns. Based on these results and other published findings, we propose that 5-HT in medial hypothalamic nuclei, in particular, the PVN, ventromedial and suprachiasmatic nuclei, acts in a phasic, circadian-related manner, specifically at the start of the active feeding cycle. At this time, it exerts its inhibitory effect primarily on the carbohydrate-rich meal that naturally occurs at dark onset and, while inducing satiety for carbohydrate, promotes the ingestion of protein in the next meal of the active cycle.