Differential expression of deltaFosB in reward processing regions between binge eating prone and resistant female rats

Abstract

Binge eating disorder (BED) is characterized by bingeing and compulsivity. Even though BED is the most prevalent eating disorder, 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 ({Delta}FosB) expression to assess chronic neuronal activation during phenotyping. The number of {Delta}FosB-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 and parabrachial nucleus); 3) higher in the paraventricular nucleus of BEP than BER rats, but not different in the locus coeruleus, which are stress processing structures. To study subtypes of {Delta}FosB-expressing neurons in the reward system, we performed in situ hybridization for glutamate decarboxylase 65 and tyrosine hydroxylase mRNA after {Delta}FosB immunohistochemistry. In the mPFC and Acb, the proportions of gamma-aminobutyric acidergic (GABAergic) and non-GABAergic {Delta}FosB-expressing neurons were similar in BER and BEP rats. In the VTA, while the proportion of dopaminergic {Delta}FosB-expressing neurons was similar in both phenotypes, the proportion of GABAergic {Delta}FosB-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.\n\nSignificanceBecause {Delta}FosB expression is associated with a reduction of activity in neurons, a higher expression of {Delta}FosB in the mPFC, Acb, and VTA of binge eating prone rats compared to binge eating resistant rats suggests a decrease in neuronal activity in these regions, which is consistent with results observed in neuroimaging studies in binge eating disorder patients. This decrease in activity due to {Delta}FosB expression may underlie the compulsivity and overconsumption of palatable food observed in both our rat model of binge-like eating and binge eating disorder patients.