Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice
Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice
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DOI：
10.1016/j.biopsych.2016.06.005
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发表时间：
2017-05-01
影响因子：
10.6
通讯作者：
Xu, Yong
中科院分区：
文献类型：
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作者：
Xu, Pingwen;He, Yanlin;Xu, Yong
背景：调控暴食的神经网络尚不清楚，有效治疗暴食的方法有限。方法：我们结合神经解剖学、药理学、电生理学、CRE-lox和化学遗传学的方法，研究了多巴胺(DA)神经元表达的5-羟色胺(5-HT2CR)2C受体(5-HT2CR)在调节小鼠暴食行为中的作用。结果：我们发现5-HT通过5-HT2CR介导的机制刺激DA神经活动，激活这个中脑5-HT-GT；DA神经回路有效地抑制小鼠暴食行为。值得注意的是，5-羟色胺药物，包括氟西汀、d-芬氟拉明和氯酪蛋白(一种选择性的5-HT2CR激动剂)，作用于DA神经元表达的5-HT2CR，以抑制小鼠暴饮式进食。结论：我们发现DA神经元中的5-HT2CR群体是抗暴食治疗的潜在靶点，并提供了临床前证据，5-HT2CR激动剂可用于治疗暴饮暴食。
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.