MEDIAL HYPOTHALAMIC NUCLEI MEDIATE SEROTONINS INHIBITORY EFFECT ON FEEDING-BEHAVIOR

Previous studies have demonstrated that injection of serotonin (5-HT) into the paraventricular nucleus (PVN), specifically at the onset of the active feeding cycle, causes a strong and selective suppression of carbohydrate intake, while producing no change in fat intake and, in some cases, enhancing protein consumption. The purpose of the present investigation was to determine whether this selective inhibitory effect of 5-HT on macronutrient ingestion is localized to a specific brain region, perhaps the PVN, or whether it can also occur in other sites throughout the hypothalamus or in regions outside this structure. A total of 7 hypothalamic and 5 extrahypothalamic areas were examined in brain-cannulated, freely feeding rats maintained on pure macronutrient diets of protein, carbohydrate and fat. The effect of 5-HT, a selective suppression (-55%) of carbohydrate feeding, was replicated in the PVN with a relatively low dose of 2.5 nmoles. Tests in 11 other brain sites demonstrated that this action of 5-HT is not unique to the PVN but is anatomically localized to the medial nuclei of the hypothalamus. Sites outside the hypothalamus, namely, the amygdala, nucleus accumbens, septum, diagonal band of Broca and nucleus reuniens dorsal to the PVN, failed to exhibit any response to 5-HT injection. Within the hypothalamus, the ventromedial (VMN) and suprachiasmatic (SCN) nuclei each responded to 5-HT in a manner similar to the PVN, producing a suppression of carbohydrate intake (-50% to -70%) with little or no change in either protein, fat or total kcal intake. The dorsomedial nucleus showed a somewhat smaller response relative to these other medial hypothalamic areas. However, other hypothalamic sites, located caudal (posterior hypothalamus), rostral (medial preoptic area), and lateral (perifornical hypothalamus at different anterior-posterior levels) to these medial nuclei, were unresponsive. Based on these results and other published findings, it is proposed that the serotonergic system for inhibiting feeding exists within the medial portion of the hypothalamus, in contrast to lateral hypothalamic or extrahypothalamic regions, and these medial hypothalamic nuclei interact closely in coordinating temporal patterns of macronutrient ingestion, possibly with the PVN and VMN serving to couple the endogenous circadian generator of the SCN to the effector feeding systems.