Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake

Abstract

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_2CR) improve obesity. Here we probed the functional significance of 5-HT_2CRs specifically within the brainstem nucleus of the solitary tract (5-HT_2CR^NTS) in feeding behavior. Selective activation of 5-HT_2CR^NTS decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HT_2CR 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_2CRs and were activated by 5-HT_2CR 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_2CR^NTS as a sufficient subpopulation of 5-HT_2CRs in reducing food intake when activated and reveal that 5-HT_2CR agonist obesity medications require POMC within the NTS and ARC to reduce food intake.