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Title: Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice

Author
item XU, PINGWEN - Children'S Nutrition Research Center (CNRC)
item HE, YANLIN - Children'S Nutrition Research Center (CNRC)
item CAO, XUEHONG - Children'S Nutrition Research Center (CNRC)
item VALENCIA-TORRES, LOURDES - Rowett Research Institute
item YAN, XIAOFENG - Children'S Nutrition Research Center (CNRC)
item SAITO, KENJI - Children'S Nutrition Research Center (CNRC)
item WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC)
item YANG, YONGJIE - Children'S Nutrition Research Center (CNRC)
item HINTON, ANTENTOR - Children'S Nutrition Research Center (CNRC)
item ZHU, LIANGRU - Children'S Nutrition Research Center (CNRC)
item SHU, GANG - Children'S Nutrition Research Center (CNRC)
item MYERS, MARTIN - University Of Michigan
item WU, QI - Children'S Nutrition Research Center (CNRC)
item TONG, QINGCHUN - University Of Texas Health Science Center
item HEISLER, LORA - Rowett Research Institute
item XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Biological Psychiatry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/3/2016
Publication Date: 8/8/2016
Citation: Xu, P., He, Y., Cao, X., Valencia-Torres, L., Yan, X., Saito, K., Wang, C., Yang, Y., Hinton, A., Zhu, L., Shu, G., Myers, M.G., Wu, Q., Tong, Q., Heisler, L., Xu, Y. 2016. Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice. Biological Psychiatry. 81:737-747.

Interpretive Summary: Binge eating is a serious medical condition, but treatment is limited. Here we showed that serotonin compounds can substantially suppress binge-like eating in mice. We further demonstrated that serotonin actions are mediated by a specific serotonin receptor expressed by brain dopamine neurons. These findings highlighted serotonin receptors expressed by dopamine neurons as the key regulator of binge eating behavior, and it could be a potential target for development of novel therapies for binge eating in humans.

Technical Abstract: Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT2CR) expressed by dopamine (DA) neurons in the regulation of binge-like eating behavior in mice. We showed that 5-HT stimulates DA neural activity through a 5-HT2CR-mediated mechanism, and activation of this midbrain 5-HT'DA neural circuit effectively inhibits binge-like eating behavior in mice. Notably, 5-HT medications, including fluoxetine, d-fenfluramine, and lorcaserin (a selective 5-HT2CR agonist), act on 5-HT2CRs expressed by DA neurons to inhibit binge-like eating in mice. We identified the 5-HT2CR population in DA neurons as one potential target for antibinge therapies, and provided preclinical evidence that 5-HT2CR agonists could be used to treat binge eating.