Nucleus of the Solitary Tract Serotonin 5-HT(2C) Receptors Modulate Food Intake

To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT(2C)R) improve obesity. Here we probed the functional significance of 5-HT(2C)Rs specifically within the brainstem nucleus of the solitary tract (5-HT(2C)R(NTS)) in feeding behavior. Selective activation of 5-HT(2C)R(NTS) decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HT(2C)R agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMC(ARC)), a subset of POMC(NTS) neurons co-expressed 5-HT(2C)Rs and were activated by 5-HT(2C)R agonists. Knockdown of POMC(NTS) prevented the acute appetite-suppressive effect of lorcaserin, whereas POMC(ARC) knockdown prevented the full anorectic effect. These data identify 5-HT(2C)R(NTS) as a sufficient subpopulation of 5-HT(2C)Rs in reducing food intake when activated and reveal that 5-HT(2C)R agonist obesity medications require POMC within the NTS and ARC to reduce food intake.