Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

  • Biol Psychiatry. 2017 May 1;81(9):737-747. doi: 10.1016/j.biopsych.2016.06.005.
Pingwen Xu  1 ,  Yanlin He  1 ,  Xuehong Cao  1 ,  Lourdes Valencia-Torres  2 ,  Xiaofeng Yan  1 ,  Kenji Saito  1 ,  Chunmei Wang  1 ,  Yongjie Yang  1 ,  Antentor Hinton Jr  1 ,  Liangru Zhu  3 ,  Gang Shu  1 ,  Martin G Myers Jr  4 ,  Qi Wu  1 ,  Qingchun Tong  5 ,  Lora K Heisler  2 ,  Yong Xu  6
Affiliations
  • 1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • 2. Rowett Institute of Nutrition and Health, Foresterhill, Aberdeen, United Kingdom.
  • 3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China.
  • 4. Department of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
  • 5. Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
  • 6. Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Children's Nutrition Research Center, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas. Electronic address: [email protected].
PMID: 27516377 DOI: 10.1016/j.biopsych.2016.06.005
Abstract

Background: Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords
Binge eating; Dopamine; Lorcaserin; Neuron; Receptor; Serotonin.
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