Differential Expression of DeltaFosB in Reward Processing Regions Between Binge Eating Prone and Resistant Female Rats.

Richard Quansah Amissah,Igor Timofeev,Genevieve Guèvremont,Juliane Calvez,Elena Timofeeva,Sandrine Chometton

doi:10.3389/fnsys.2020.562154

Abstract

Binge eating (BE) is characterized by the consumption of large amounts of palatable food in a discrete period and compulsivity. Even though BE is a common symptom in bulimia nervosa (BN), binge eating disorder (BED), and some cases of other specified feeding or eating disorders, little is known about its pathophysiology. We aimed to identify brain regions and neuron subtypes implicated in the development of binge-like eating in a female rat model. We separated rats into binge eating prone (BEP) and binge eating resistant (BER) phenotypes based on the amount of sucrose they consumed following foot-shock stress. We quantified deltaFosB (ΔFosB) expression, a stably expressed Fos family member, in different brain regions involved in reward, taste, or stress processing, to assess their involvement in the development of the phenotype. The number of ΔFosB-expressing neurons was: (1) higher in BEP than BER rats in reward processing areas [medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA)]; (2) similar in taste processing areas [insular cortex, IC and parabrachial nucleus (PBN)]; and (3) higher in the paraventricular nucleus of BEP than BER rats, but not different in the locus coeruleus (LC), which are stress processing structures. To study subtypes of ΔFosB-expressing neurons in the reward system, we performed in situ hybridization for glutamate decarboxylase 65 and tyrosine hydroxylase (TH) mRNA after ΔFosB immunohistochemistry. In the mPFC and Acb, the proportions of γ-aminobutyric acidergic (GABAergic) and non-GABAergic ΔFosB-expressing neurons were similar in BER and BEP rats. In the VTA, while the proportion of dopaminergic ΔFosB-expressing neurons was similar in both phenotypes, the proportion of GABAergic ΔFosB-expressing neurons was higher in BER than BEP rats. Our results suggest that reward processing brain regions, particularly the VTA, are important for the development of binge-like eating.

Highlights

Eating disorders, namely anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding or eating disorders (OSFEDs), cause severe disturbances to eating habits (Galmiche et al, 2019)
We found that the number of cells expressing both glutamic acid decarboxylase 65 (GAD65) mRNA and ∆FosB was higher in the accumbens core (AcbC) (Figure 7A) and accumbens shell (AcbSh) (Figure 7C) in binge eating prone (BEP) compared to binge eating resistant (BER) rats
Binge-like eating rats in this study consumed a large amount of palatable food and bingeing was triggered by stress, which suggests that reward, taste, and stress processing brain regions may be involved (Wolff et al, 2000; American Psychiatric Association, 2013)

Summary

Introduction

Namely anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding or eating disorders (OSFEDs), cause severe disturbances to eating habits (Galmiche et al, 2019). While several neuroimaging studies, using functional magnetic resonance imaging (fMRI) in humans, showed that BE is associated with increased fMRI activity in the reward system (Karhunen et al, 2000; Schafer et al, 2010; Filbey et al, 2012; Tanofsky-Kraff et al, 2013; Lee et al, 2017), others reported decreased fMRI activity in this system (Balodis et al, 2013, 2014; Halpern et al, 2013; Reiter et al, 2017) It is unclear whether BE is associated with increased or decreased reward system activity and whether other systems could be involved. This important knowledge will help develop efficient therapies that could target specific neuron populations in the different brain regions that form the reward system

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