Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
Physiol Behav. 2023 Nov 1;271:114349. doi: 10.1016/j.physbeh.2023.114349. Epub 2023 Sep 12.
Individuals with anorexia nervosa (AN) exhibit dangerous weight loss due to restricted eating and hyperactivity. Those with AN are predominantly women and most cases have an age of onset during adolescence. Activity-based anorexia (ABA) is a rodent behavioral paradigm that recapitulates many of the features of AN including restricted food intake and hyperactivity, resulting in precipitous weight loss. In addition, there is enhanced sensitivity to the paradigm during adolescence. In ABA, animals are given time-restricted access to food and unlimited access to a running wheel. Under these conditions, most animals increase their running and decrease their food intake resulting in precipitous weight loss until they either die or researchers discontinue the paradigm. Some animals learn to balance their food intake and energy expenditure and are able to stabilize and eventually reverse their weight loss. For these studies, adolescent (postnatal day 33-42), female Sprague Dawley (n = 68) rats were placed under ABA conditions (unlimited access to a running wheel and 1.5 hrs access to food) until they either reached 25% body weight loss or for 7 days. 70.6% of subjects reached 25% body weight loss before 7 days and were designated susceptible to ABA while 29.4% animals were resistant to the paradigm and did not achieve the weight loss criterion. We used discrete time survival analysis to investigate the contribution of food intake and running behavior during distinct time periods both prior to and during ABA to the likelihood of reaching the weight loss criterion and dropping out of ABA. Our analyses revealed risk factors, including total running and dark cycle running, that increased the likelihood of dropping out of the paradigm, as well as protective factors, including age at the start of ABA, the percent of total running exhibited as food anticipatory activity (FAA), and food intake, that reduced the likelihood of dropping out. These measures had predictive value whether taken before or during exposure to ABA conditions. Our findings suggest that certain running and food intake behaviors may be indicative of a phenotype that predisposes animals to susceptibility to ABA. They also provide evidence that running during distinct time periods may reflect functioning of distinct neural circuitry and differentially influence susceptibility and resistance to the paradigm.
患有神经性厌食症（AN）的个体因进食受限和过度活跃而出现危险的体重减轻。患有 AN 的个体主要为女性，大多数病例的发病年龄在青春期。活动性厌食症（ABA）是一种啮齿动物行为范式，可重现 AN 的许多特征，包括限制食物摄入和过度活跃，导致体重迅速下降。此外，在青春期期间对该范式的敏感性增强。在 ABA 中，动物被给予限时进食和无限期使用跑步轮的机会。在这些条件下，大多数动物会增加跑步量并减少食物摄入量，从而导致体重迅速下降，直到它们死亡或研究人员停止该范式。一些动物学会平衡食物摄入和能量消耗，能够稳定下来，并最终逆转体重减轻。对于这些研究，将青春期（出生后第 33-42 天）、雌性 Sprague Dawley（n=68）大鼠置于 ABA 条件下（无限期使用跑步轮和 1.5 小时进食机会），直到它们体重减轻达到 25%或持续 7 天。70.6%的动物在 7 天前体重减轻达到 25%，被指定为对 ABA 敏感，而 29.4%的动物对该范式具有抗性，并且没有达到体重减轻的标准。我们使用离散时间生存分析来研究在 ABA 之前和期间的不同时间段内，食物摄入量和跑步行为对达到体重减轻标准和退出 ABA 的可能性的贡献。我们的分析揭示了风险因素，包括总跑步量和暗周期跑步量，这些因素增加了退出范式的可能性，以及保护因素，包括 ABA 开始时的年龄、作为食物预期活动（FAA）表现的总跑步量的百分比以及食物摄入量，这些因素降低了退出的可能性。这些措施在接触 ABA 条件之前或期间均具有预测价值。我们的研究结果表明，某些跑步和食物摄入行为可能表明易感性动物对 ABA 易感性的表型。它们还提供了证据表明，在不同时间段内的跑步可能反映了不同的神经回路的功能，并对该范式的易感性和抗性产生不同的影响。
