Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice

Sci Rep. 2021 Jun 18;11(1):12873. doi: 10.1038/s41598-021-92386-7.

Abstract

The reward system, which consists of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and caudate-putamen in the striatum, has an important role in the pathogenesis of not only drug addiction but also diet-induced obesity. In the present study, we examined whether signaling through glucocorticoid receptors (GRs) in the reward system affects the rewarding value of a high-fat diet (HFD). To do so, we generated mice that lack functional GRs specifically in dopaminergic neurons (D-KO mice) or corticostriatal neurons (CS-KO mice), subjected the mice to caloric restriction stress conditions, and evaluated the rewarding value of a HFD by conditioned place preference (CPP) test. Caloric restriction induced increases in serum corticosterone to similar levels in all genotypes. While CS-KO as well as WT mice exhibited a significant preference for HFD in the CPP test, D-KO mice exhibited no such preference. There were no differences between WT and D-KO mice in consumption of HFD after fasting or cognitive function evaluated by a novel object recognition test. These data suggest that glucocorticoid signaling in the VTA increases the rewarding value of a HFD under restricted caloric stress.

MeSH terms

  • Animals
  • Conditioning, Classical
  • Diet, High-Fat*
  • Dopaminergic Neurons / metabolism
  • Energy Metabolism
  • Fasting
  • Gene Expression
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Neurons / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Reward*
  • Signal Transduction*
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism*

Substances

  • Receptors, Glucocorticoid