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

Pingwen Xu, Yanlin He, Xuehong Cao, Lourdes Valencia-Torres, Xiaofeng Yan, Kenji Saito, Chunmei Wang, Yongjie Yang, Antentor Hinton Jr., Liangru Zhu, Gang Shu, Martin G. Myers Jr., Qi Wu, Qingchun Tong, Lora K. Heisler, Yong Xu

Research output: Contribution to journalArticle

36 Citations (Scopus)
9 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)737-747
Number of pages11
JournalBiological Psychiatry
Volume81
Issue number9
Early online date9 Jun 2016
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • binge eating
  • dopamine
  • lorcaserin
  • receptor
  • neuron
  • serotonin

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