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

doi:10.1016/j.biopsych.2016.06.005

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. Epub 2016 Jun 9.

Authors

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].

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-HT_2CR) 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-HT_2CR-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-HT_2CR agonist), act on 5-HT_2CRs expressed by DA neurons to inhibit binge-like eating in mice.

Conclusions: We identified the 5-HT_2CR population in DA neurons as one potential target for antibinge therapies, and provided preclinical evidence that 5-HT_2CR agonists could be used to treat binge eating.

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

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Benzazepines / administration & dosage
Bulimia / metabolism
Bulimia / physiopathology*
Dopaminergic Neurons / drug effects
Dopaminergic Neurons / metabolism*
Eating / drug effects
Female
Fluoxetine / administration & dosage
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Receptor, Serotonin, 5-HT2C / metabolism*
Selective Serotonin Reuptake Inhibitors / administration & dosage
Ventral Tegmental Area / drug effects
Ventral Tegmental Area / physiopathology*

Substances

Benzazepines
Receptor, Serotonin, 5-HT2C
Serotonin Uptake Inhibitors
Fluoxetine
lorcaserin

Abstract

Publication types

MeSH terms

Substances

Grants and funding