Xu, YongJones, Juli E.Kohno, DaisukeWilliams, Kevin W.Choi, Michelle J.Anderson, Jason G.Heisler, Lora K.Zigman, Jeffrey M.Elmquist, Joel K.Lee, Charlotte E.Lowell, Bradford2012-02-192008Xu, Yong, Juli E. Jones, Daisuke Kohno, Kevin W. Williams, Charlotte E. Lee, Michelle J. Choi, Jason G. Anderson, et al. 2008. 5-HT\(_{\text{2C}}\)Rs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron 60(4): 582-589.0896-6273http://nrs.harvard.edu/urn-3:HUL.InstRepos:8191178Drugs activating 5-hydroxytryptamine 2C receptors (5-HT\(_{\text{2C}}\)Rs) potently suppress appetite, but the underlying mechanisms for these effects are not fully understood. To tackle this issue, we generated mice with global 5-HT\(_{\text{2C}}\)Rs deficiency (2C null) and mice with 5-HT\(_{\text{2C}}\)Rs re-expression only in pro-opiomelanocortin (POMC) neurons (2C/POMC mice). We show that 2C null mice predictably developed hyperphagia, hyperactivity, and obesity and showed attenuated responses to anorexigenic 5-HT drugs. Remarkably, all these deficiencies were normalized in 2C/POMC mice. These results demonstrate that 5-HT\(_{\text{2C}}\)R expression solely in POMC neurons is sufficient to mediate effects of serotoninergic compounds on food intake. The findings also highlight the physiological relevance of the 5-HT\(_{\text{2C}}\)R-melanocortin circuitry in the long-term regulation of energy balance.en-UShumdiseasemolneurosignalingJournal Article10.1016/j.neuron.2008.09.033