Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa

Authors

Jeff A. Beeler, CUNY Queens CollegeFollow
Devry Mourra, CUNY Queens CollegeFollow
Roseanna M. Zanca, CUNY Graduate CenterFollow
Abigail Kalmbach, Columbia University
Celia Gellman, Columbia University
Benjamin Y. Klein, Columbia University
Rebecca Ravenelle, CUNY Graduate CenterFollow
Peter Serrano, CUNY Graduate CenterFollow
Holly Moore, Columbia University
Stephen Rayport, Columbia University
Susana Mingote, CUNY Advanced Science Research CenterFollow
Nesha Burghard, CUNY Hunter CollegeFollow

Document Type

Article

Publication Date

2021

Abstract

Background

Increased physical activity is a common feature of anorexia nervosa (AN). Although high activity levels are associated with greater risk of developing AN, particularly when combined with dieting, most individuals who diet and exercise maintain a healthy body weight. It is unclear why some individuals develop AN while most do not. A rodent model of resilience and vulnerability to AN would be valuable to research. Dopamine, which is believed to play a crucial role in AN, regulates both reward and activity and may modulate vulnerability.

Methods

Adolescent and young adult female C57BL/6N mice were tested in the activity-based anorexia (ABA) model, with an extended period of food restriction in adult mice. ABA was also tested in dopamine transporter knockdown mice and wild-type littermates. Mice that adapted to conditions and maintained a stable body weight were characterized as resilient.

Results

In adults, vulnerable and resilient phenotypes emerged in both the ABA and food-restricted mice without wheels. Vulnerable mice exhibited a pronounced increase in running throughout the light cycle, which dramatically peaked prior to requiring removal from the experiment. Resilient mice exhibited an adaptive decrease in total running, appropriate food anticipatory activity, and increased consumption, thereby achieving stable body weight. Hyperdopaminergia accelerated progression of the vulnerable phenotype.

Conclusions

Our demonstration of distinct resilient and vulnerable phenotypes in mouse ABA significantly advances the utility of the model for identifying genes and neural substrates mediating AN risk and resilience. Modulation of dopamine may play a central role in the underlying circuit.

Comments

This article was originally published in Biological Psychiatry, available at https://doi.org/10.1016/j.biopsych.2020.06.030

This work is distributed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).