Nucleus of the Solitary Tract Serotonin 5-HT 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-HTR) improve obesity. Here we probed the functional significance of 5-HTRs specifically within the brainstem nucleus of the solitary tract (5-HTR) in feeding behavior. Selective activation of 5-HTR decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HTR agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMC), a subset of POMC neurons co-expressed 5-HTRs and were activated by 5-HTR agonists. Knockdown of POMC prevented the acute appetite-suppressive effect of lorcaserin, whereas POMC knockdown prevented the full anorectic effect. These data identify 5-HTR as a sufficient subpopulation of 5-HTRs in reducing food intake when activated and reveal that 5-HTR agonist obesity medications require POMC within the NTS and ARC to reduce food intake.