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.
Biol Psychiatry. 2021 Dec 15;90(12):829-842. doi: 10.1016/j.biopsych.2020.06.030. Epub 2020 Jul 16.
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.
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.
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.
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.
增加身体活动是神经性厌食症（AN）的常见特征。尽管高活动水平与更高的 AN 发病风险相关，尤其是与节食相结合时，但大多数节食和运动的人仍能保持健康的体重。目前尚不清楚为什么有些个体发展为 AN，而大多数个体没有。一种对 AN 具有韧性和脆弱性的啮齿动物模型将对研究很有价值。多巴胺被认为在 AN 中起关键作用，它调节奖励和活动，并且可能调节脆弱性。
在基于活动的厌食症（ABA）模型中测试了青春期和成年早期的雌性 C57BL/6N 小鼠，成年小鼠进行了延长的食物限制。还在多巴胺转运蛋白敲低小鼠和野生型同窝仔鼠中测试了 ABA。适应条件并保持稳定体重的小鼠被认为是有韧性的。
在成年小鼠中，ABA 和无轮食物限制的小鼠中出现了脆弱和有韧性的表型。脆弱型小鼠在整个光照周期内表现出明显的跑步量增加，在需要从实验中移除之前急剧增加。有韧性的小鼠表现出总跑步量适应性减少、适当的食物预期活动和增加的消耗，从而实现稳定的体重。多巴胺能亢进加速了脆弱表型的进展。
我们在小鼠 ABA 中观察到明显的有韧性和脆弱表型，这极大地提高了该模型用于识别介导 AN 风险和韧性的基因和神经基质的效用。多巴胺的调节可能在潜在的回路中起核心作用。
