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.

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.

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*
  • Serotonin Uptake Inhibitors / administration & dosage
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiopathology*

Substances

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