Shifts in Naturalistic Behaviors Induced by Early Social Isolation Stress are Associated with Adult Binge-like Eating in Female Rats

Simon, T. B.; Sierra, J.; Williams, A.; Wright, G.; Rhee, A.; Horn, J.; Lou, J.; Sharafeddin, F.; Ontiveros-Angel, P.; Figueroa, J. D.

doi:10.1101/2024.10.28.620673

bioRxiv · 10.1101/2024.10.28.620673

Shifts in Naturalistic Behaviors Induced by Early Social Isolation Stress are Associated with Adult Binge-like Eating in Female Rats

Simon, T. B.·Sierra, J.·Williams, A.·Wright, G.·Rhee, A.·Horn, J.·Lou, J.·Sharafeddin, F.·Ontiveros-Angel, P.·Figueroa, J. D.

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Abstract

Binge eating (BE) is a highly pervasive maladaptive coping strategy in response to severe early life stress such as emotional and social neglect. BE is described as repeated episodes of uncontrolled eating and is tightly linked with comorbid mental health concerns. Despite social stressors occurring at a young age, the onset of BE typically does not occur until adulthood providing an interval for potential therapeutic intervention. Currently, our knowledge of longitudinal noninvasive digital biomarkers predictive of BE needs further development. Monitoring longitudinal impacts of adolescent social isolation stress on naturalistic behaviors in rats will enable the identification of noninvasive digital markers of disease progression to predict adult eating strategies. Recognizing adolescent naturalistic behaviors shaped by social stress informs our understanding of the underlying neurocircuits most effected. This study aimed to monitor and identify longitudinal behavioral shifts to enhance predictive capabilities in a rat model of social isolation stress-induced BE. We placed Paired (n=12) and Socially Isolated (SI, n=12) female rats in observational home cages weekly for seven weeks to evaluate the effect of SI on 10 naturalistic behaviors. All 10 naturalistic behaviors were simultaneously detected and tracked using Noldus Ethovision XT automated recognition software. Composite phenotypic z-scores were calculated by standardizing all 10 behaviors. When transitioning into adulthood, all rats underwent conventional emotionality testing and were exposed to a Western-like high fat diet (WD, 43% kcal from fat) to evaluate BE. Longitudinal assessments revealed SI-induced shifts in adolescent phenotypic z-scores and that sniffing, unsupported rearing, jumping, and twitching were the most susceptible to SI. SI increased emotionality compared to the Paired controls. Finally, we identified adolescent twitching as a digital biomarker of adult WD consumption. This study employed novel approaches to identify early life predictive biomarkers of adult eating strategies and laid a foundation for future investigations.

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Simon, T. B., Sierra, J., Williams, A., Wright, G., Rhee, A., Horn, J., Lou, J., Sharafeddin, F., Ontiveros-Angel, P., Figueroa, J. D.. 2024-10-28. Shifts in Naturalistic Behaviors Induced by Early Social Isolation Stress are Associated with Adult Binge-like Eating in Female Rats. https://doi.org/10.1101/2024.10.28.620673

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