GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice

Runan Sun,Taku Tsunekawa,Hiroshi Takagi,Tomonori Hirose,Shintaro Iwama,Hidetaka Suga,Akira Mizoguchi,Tomoko Kobayashi,Keigo Taki,Hiroshi Arima,Ryoichi Banno,Bernhard Bettler,Daisuke Hagiwara,Takashi Miyata,Hiroshi Yaginuma,Mariko Sugiyama,Takeshi Onoue,Yoshihiro Ito

doi:10.1038/s41598-021-98590-9

Abstract

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

Highlights

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity
We showed that drd1-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) were significantly activated in WT mice after binge-like consumption on a high fat diet (HFD)
Our data showed that activation of drd1expressing neurons was significantly enhanced in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient mice compared to WT mice after binge-like consumption on a HFD

Summary

Introduction

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. We show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. Baclofen suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Intermittent access to a HFD reportedly causes binge-like eating behavior in a rodent model, as shown by increases in the motivation to consume[8] and gradual increases in consumption[9,10] These behaviors are accompanied by the activation of neurons in the VTA as well as striatum, where an increase in extracellular dopamine concentration has been shown in a rodent model[7,11].

Methods

Results

Conclusion