Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa,Biological Psychiatry

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Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa
Biological Psychiatry ( IF 10.6 ) Pub Date : 2020-07-16 , DOI: 10.1016/j.biopsych.2020.06.030
Jeff A Beeler ₁ , Devry Mourra ₂ , Roseanna M Zanca ₃ , Abigail Kalmbach ₄ , Celia Gellman ₅ , Benjamin Y Klein ₆ , Rebecca Ravenelle ₇ , Peter Serrano ₃ , Holly Moore ₈ , Stephen Rayport ₅ , Susana Mingote ₉ , Nesha S Burghardt ₁₀

Affiliation

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.
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.
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.
Department of Psychiatry, Columbia University, New York, New York; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York.
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.
Biology Program, The Graduate Center, City University of New York, New York.
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.
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.
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.

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.

中文翻译：

神经性厌食症小鼠模型中的脆弱和弹性表型

背景

增加体力活动是神经性厌食症 (AN) 的常见特征。尽管高活动水平与发生 AN 的风险增加相关，尤其是与节食相结合时，但大多数节食和锻炼的人都保持健康的体重。目前尚不清楚为什么有些人会出现 AN 而大多数人不会。对 AN 具有弹性和脆弱性的啮齿动物模型对研究很有价值。多巴胺被认为在 AN 中起着至关重要的作用，它调节奖励和活动，并可能调节脆弱性。