Estudo da compulsão alimentar associada ao comportamento do tipo depressivo em camundongos C57BL/6 fêmeas: padronização de um protocolo experimental envolvendo estresse e acesso intermitente à sacarose

Abstract

Binge eating disorder is the most prevalent eating disorder globally, characterized by multiple physiological and neural mechanisms, including dysfunction of the monoaminergic system and the hypothalamic-pituitary-adrenal (HPA) axis. This disorder has a detrimental impact on individuals' lives and is frequently accompanied by other psychiatric conditions such as depression. Current treatments often fail to yield significant symptom improvement, underscoring the need to comprehend the intricate neuropathology of compulsive eating disorder. The objectives of this study were twofold: I) to establish a robust experimental protocol for replicating compulsive eating behavior and depressive phenotypes in animals through intermittent access to sucrose solution and food fasting, and II) to investigate potential biochemical alterations focusing on the monoaminergic system and the HPA axis. Female C57BL/6 mice were divided into four groups, matched for baseline body weight and food intake: (I) Naive - continuous access to standard chow; (II) Control - continuous access to a 10% sucrose solution and standard chow; (III) J16 - 16-hour fasting followed by 8-hour access to a 10% sucrose solution and standard chow; and (IV) J20 - 20-hour fasting followed by 4-hour access to a 10% sucrose solution and standard chow. The animals underwent induction under these conditions for 10 days. After the induction to generate compulsive-like behavior (11th day), the animals underwent the feeding test, open field test (OFT), elevated plus maze test (EPMT), tail suspension test (TST), and, on the following day (12th day), the light/dark conflict test (LDCT), followed by euthanasia. Brain structures, including the hippocampus, prefrontal cortex, and hypothalamus, were extracted to analyze the activity of monoamine oxidases (MAOs) A and B, and plasma samples were collected to measure corticosterone levels. Both fasting groups exhibited compulsive eating and depressive-like behavior, along with increased blood corticosterone levels, elevated hippocampal MAO-A activity, and decreased MAO-B activity in the prefrontal cortex and hypothalamus. Notably, only the J20 group displayed abstinence and impulsive behavior in the LDCT and EPMT tasks. Additionally, continuous sucrose exposure led to reduced locomotion in the OFT and increased prefrontal cortex MAO-A activity. In conclusion, our findings suggest that while J16 may induce comorbid behavior in female C57BL/6 mice, J20 was the most reliable method for generating binge-eating-like behavior associated with a depressive like phenotype, characterized by withdrawal from palatable food. Thus, this protocol may have future applications in evaluating potential treatments for binge eating disorder comorbid with depression.