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

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 (∆FosB) 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 ∆FosBexpressing 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 ∆FosB-expressing neurons in the reward system, we performed in situ hybridization for glutamate decarboxylase 65 and tyrosine hydroxylase (TH) mRNA after ∆FosB immunohistochemistry. In the mPFC and Acb, the proportions of γ-aminobutyric acidergic (GABAergic) and non-GABAergic ∆FosB-expressing neurons were similar in BER and BEP rats. In the VTA, while the proportion of dopaminergic ∆FosB-expressing neurons was similar in both phenotypes, the proportion of GABAergic ∆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.

Breaking It Down: Investigation of Binge Eating Components in Animal Models to Enhance Translation

“…There are individual differences in the consumption of high sweetness PF. The variability in PF intake allows for animals to be classified as BE-prone or BE-resistant based on amount of PF consumed (73,89,90) promoting the study of individual differences in BE phenotypes. Additionally, the caloric makeup of high sweetness PF does not impact binge-like eating, demonstrated by the fact that there were no differences in sucrose (caloric) or saccharin (noncaloric) consumption during a 4 h exposure (91).…”

“…Using a consistency of consumption threshold, animals that consumed high amounts of PF and consistently maintained intake of PF within 10-15% across consecutive days were identified as being in a chronic binge eating state (69)(70)(71). Groupings have also been made using statistical cutoffs (e.g., median split, tertiles) based on consistency of PF intake during a study period to identify extreme groups of BE-prone and BE-resistant animals (45,48,54,65,72,73,89,90,105). This allows for comparison between extreme BE and non-BE groups for analysis, which is translationally relevant to work comparing BE and non-BE human populations within a study (112,113).…”

“…Importantly, 2-h exposure to PF later in the dark phase, when animals are likely sated from standard chow consumption, still results in binge-like eating (93,94,98,102), suggesting that animals will engage in binge-like eating that is beyond homeostatic needs. While 2 h access schedules align with diagnostic guidance for binge-related disorders (1,40), shorter intermittent access periods of 1 h (33,63,65,69,73,89,90,100), and as short as 10 min each day (81,82), also result in significant consumption of PF in a short period of time.…”

“…The compulsive-like behavior paradigms used in preclinical approaches determine if animals that engage in bingelike eating are more likely to endure punishment or negative outcomes (e.g., foot shock) in order to receive a palatable reward (117), indicating more compulsivity and/or increased motivation to consume PF which is reflective of loss of control relevant behavior. Specifically, animals with a history of intermittent access to PF demonstrate more willingness to experience foot shock (84,86), endure repeated foot shocks increasing in intensity (54), and spend more time in the light side of a lightdark chamber where PF was presented compared to animals without a history of intermittent PF access (73,89). BE-prone animals were also more likely to continue daily consumption of PF combined with lactose (which leads to physical discomfort) compared to BE-resistant animals that reduced PF + lactose intake over time (105).…”

“…Beyond these core components, other clinical characteristics of BE have been modeled in animals. While BE in response to stress is not listed among diagnostic criteria for binge-related disorders, there is evidence that stress and negative affect may increase food intake and BE in humans (124)(125)(126)(127)(128) and animals (73,89,90,103). Additionally, caloric restriction has also been shown to increase the likelihood of BE in humans (129) and animals (130).…”