Hildebrandt, B. A. | bioRxiv Science

bioRxiv2022

Examination of Onset Trajectories and Persistence of Binge-Like Eating Behavior in Mice after Intermittent Palatable Food Exposure

Binge eating (BE) is a persistent behavior associated with a chronic course of illness and poor treatment outcomes. While clinical research is unable to capture the full course of BE, pre-clinical approaches offer the opportunity to examine binge-like eating from onset through chronic durations, allowing identification of factors contributing to BE persistence. The current study quantified the trajectories of binge-like eating onset and modeled cycles of abstinence/relapse to develop a translational model for BE persistence. Adult male and female C57Bl6/J mice were randomized to a binge-like palatable food (PF) access schedule (daily 2-hour, 3x/week) or continuous, non-binge like PF access for 12 days (Experiment 1). Persistence of PF consumption in both binge-like PF access groups was then examined across three cycles of forced abstinence and re-exposure to PF (incubation) to model the persistence of BE in clinical populations. Mice with daily 2 hour PF access escalated their intake more than mice in the 3x/week or continuous groups (Experiment 1).This pattern was more pronounced in females. In addition, this pattern of PF intake re-emerged across multiple cycles of behavioral incubation (Experiment 2). These findings provide a model of binge-like eating in mice that can be used in future studies examining both environmental factors and neural mechanisms contributing to BE persistence.

neuroscience↗

bioRxiv2021

Corticostriatal dynamics underlying components of binge-like eating in mice

Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. Despite the substantial negative impact of BE on psychological and physiological health, its underlying neural mechanisms are largely unknown. Other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. Additionally, previous pre-clinical and clinical work has highlighted an imbalance between goal-directed and habitual responding in BE. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions associated with habitual behavior- the infralimbic cortex (IL) and dorsolateral striatum (DLS)- in a robust pre-clinical model for BE. Female C57BL/6 mice (N=32) were randomized to receive: 1) intermittent (daily, 2-hour) binge-like access to palatable food (BE mice), or 2) continuous, non-intermittent (24-hour) access to palatable food (non-BE mice). In vivo calcium imaging was performed via fiber photometry at baseline and after chronic (4 weeks) engagement in the model for BE. Feeding behaviors (feeding bout onset/offset) during the recordings were captured using lickometers which generated TTL outputs for precise alignment of behavior to neural data. IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity at feeding onset and offset at the chronic timepoint when compared to baseline. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset at the chronic timepoint compared to non-BE mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention. Significance StatementBinge eating is a chronic and repetitive eating behavior that is associated with poor physiological and psychosocial outcomes. Despite the negative impact of binge eating, little is known about the neurobiological mechanisms contributing to the chronic course and persistence of the behavior. To investigate potential neural mechanisms underlying binge eating, we are using approaches developed to monitor neural activity in rodents. This study is the first to identify longitudinal changes in neural activity within regions of the prefrontal cortex and dorsal striatum during binge-like eating behavior in mice. Findings from this work could inform targeted biological treatments for binge eating.

neuroscience↗