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

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^* (Corresponding Author)

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

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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 language	English
Pages (from-to)	737-747
Number of pages	11
Journal	Biological Psychiatry
Volume	81
Issue number	9
Early online date	9 Jun 2016
DOIs	https://doi.org/10.1016/j.biopsych.2016.06.005
Publication status	Published - 1 May 2017

Bibliographical note

Acknowledgments and Disclosures

This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064.

PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors report no biomedical financial interests or potential conflicts of interest.

Keywords

binge eating
dopamine
lorcaserin
receptor
neuron
serotonin

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10.1016/j.biopsych.2016.06.005Licence: CC BY

Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice
& 2016 Society of Biological Psychiatry. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Final published version, 6.3 MBLicence: CC BY

Lora Heisler
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Chair in Human Nutrition
Person: Academic

Cite this

@article{ccdb1bbbc28b45489f3771f61ca3a1ec,

title = "Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice",

abstract = "BackgroundNeural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited.MethodsWe 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.ResultsWe 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.ConclusionsWe 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, receptor, neuron, serotonin",

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

note = "Acknowledgments and Disclosures This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.",

year = "2017",

month = may,

day = "1",

doi = "10.1016/j.biopsych.2016.06.005",

language = "English",

volume = "81",

pages = "737--747",

journal = "Biological Psychiatry",

issn = "0006-3223",

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number = "9",

}

TY - JOUR

T1 - Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

AU - Xu, Pingwen

AU - He, Yanlin

AU - Cao, Xuehong

AU - Valencia-Torres, Lourdes

AU - Yan, Xiaofeng

AU - Saito, Kenji

AU - Wang, Chunmei

AU - Yang, Yongjie

AU - Hinton Jr., Antentor

AU - Zhu, Liangru

AU - Shu, Gang

AU - Myers Jr., Martin G.

AU - Wu, Qi

AU - Tong, Qingchun

AU - Heisler, Lora K.

AU - Xu, Yong

N1 - Acknowledgments and Disclosures This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - BackgroundNeural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.

AB - BackgroundNeural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.

KW - binge eating

KW - dopamine

KW - lorcaserin

KW - receptor

KW - neuron

KW - serotonin

U2 - 10.1016/j.biopsych.2016.06.005

DO - 10.1016/j.biopsych.2016.06.005

M3 - Article

SN - 0006-3223

VL - 81

SP - 737

EP - 747

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 9

ER -

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

Abstract

Bibliographical note

Keywords

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Lora Heisler

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