期刊
BIOLOGICAL PSYCHIATRY
卷 81, 期 9, 页码 737-747出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2016.06.005
关键词
Binge eating; Dopamine; Lorcaserin; Neuron; Receptor; Serotonin
资金
- National Institutes of Health [R01DK093587, R01DK101379, R01DK092605, R01DK078056, P30HD024064]
- Klarman Family Foundation
- Naman Family Fund for Basic Research
- Curtis Hankamer Basic Research Fund
- American Diabetes Association [7-13-JF-61, 1-15-BS-184]
- American Heart Association postdoctoral fellowship
- Wellcome Trust [WT098012]
- Biotechnology and Biological Sciences Research Council [BB/K001418/1]
- Biotechnology and Biological Sciences Research Council [BB/K001418/1] Funding Source: researchfish
- BBSRC [BB/K001418/1] Funding Source: UKRI
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.
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