Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa

Jeff A Beeler; Devry Mourra; Roseanna M Zanca; Abigail Kalmbach; Celia Gellman; Benjamin Y Klein; Rebecca Ravenelle; Peter Serrano; Holly Moore; Stephen Rayport; Susana Mingote; Nesha S Burghardt

doi:10.1016/j.biopsych.2020.06.030

Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa

Biol Psychiatry. 2021 Dec 15;90(12):829-842. doi: 10.1016/j.biopsych.2020.06.030. Epub 2020 Jul 16.

Authors

Affiliations

¹ Department of Psychology, Queens College, City University of New York, Flushing, New York; Psychology Program, The Graduate Center, City University of New York, New York, New York; Biology Program, The Graduate Center, City University of New York, New York. Electronic address: jbeeler@qc.cuny.edu.
² Department of Psychology, Queens College, City University of New York, Flushing, New York; Psychology Program, The Graduate Center, City University of New York, New York, New York.
³ Psychology Program, The Graduate Center, City University of New York, New York, New York; Department of Psychology, Hunter College, City University of New York, New York.
⁴ Department of Psychiatry, Columbia University, New York, New York.
⁵ Department of Psychiatry, Columbia University, New York, New York; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York.
⁶ Department of Psychiatry, Columbia University, New York, New York; Developmental Neuroscience, New York State Psychiatric Institute, New York, New York; Department of Microbiology and Molecular Genetics, Hebrew University, Jerusalem, Israel.
⁷ Biology Program, The Graduate Center, City University of New York, New York.
⁸ Department of Psychiatry, Columbia University, New York, New York; Integrative Neuroscience, New York State Psychiatric Institute, New York, New York; National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
⁹ Department of Psychiatry, Columbia University, New York, New York; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York; Advanced Science Research Center, The Graduate Center, City University of New York, New York.
¹⁰ Psychology Program, The Graduate Center, City University of New York, New York, New York; Department of Psychology, Hunter College, City University of New York, New York; Department of Psychiatry, Columbia University, New York, New York. Electronic address: nb844@hunter.cuny.edu.

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.

Keywords: Activity-based anorexia; Anorexia nervosa; Dopamine; Exercise; Food restriction; Hyperdopaminergic; Resilience; Starvation; Vulnerability.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anorexia
Anorexia Nervosa* / genetics
Disease Models, Animal
Female
Mice
Mice, Inbred C57BL
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding