Druggable 5-HT Receptors for Obesity

          Pharmacological agents that boost brain serotonin (5-HT) signaling reduce food intake. The therapeutic potential of this pathway was highlighted by the demonstration that the appetite-suppressant effect of 5-HT was, in part due to the activation of serotonin 2c receptors (Htr2c). Subsequently, lorcaserin, a specific HTR2c agonist became a novel weight-loss medication in 2012.

          In addition to Htr2c, agonists for the 5-HT 1b (Htr1b) along with antagonists for the 5-HT 6 (Htr6) receptors also suppress appetite.  These observations suggest that the two receptors are potentially new druggable targets to combat the obesity epidemic.  In the lab, we have developed a series of mouse genetic tools to map the functional 5-HT1b and 5-HT6 circuits underlying appetite control.