Valencia-Flores Kenji B, Vidal-de-laO Yahel, Paz-Trejo Diana, Sánchez-Castillo Hugo
Psychology School, Psychobiology and Neurosciences Department, Universidad Nacional Autónoma de México, Mexico.
Iberoamerican Society of Applied Neuroscience, Mexico.
IBRO Neurosci Rep. 2025 May 10;18:803-813. doi: 10.1016/j.ibneur.2025.05.001. eCollection 2025 Jun.
Chronic stress during life has been considered a risk factor for the development of psychiatric illness in humans. Chronic unpredictable stress battery (CUSB) is an animal model to study depression through stress exposition in rodents. CUSB induces depression and anxiety behavioral markers that could be modulated with fluoxetine an antidepressant treatment. However, it is well known that not all subjects develop depression-like behaviors or do not respond to antidepressant treatments. The way to screen these individual differences in susceptibility to stress or the efficacy of antidepressant therapy in depression models is not well studied. Here we show that saccharine consumption, immobility and time spent in the center of the area could be useful as behavioral markers for screening susceptibility to stress and depression, also we show that fluoxetine treatment had different efficacy depending on the age when the stress occurred. First, we found that after CUSB (during adolescence, adulthood, or both) rodents show depression and anxiety profiles. Second, we found that fluoxetine (10 mg/kg) could recover depression but no anxiety profile in all the groups exposed to stress. Finally, we use the machine learning clustering method (k-means), to classify the subjects in all groups based on the individual effects modulated by stress exposure and antidepressant treatment to find the ratio of stress effects and pharmacological efficacy. Using altered behaviors as classifiers, we found three possible clusters, (1) Without alterations, (2) Moderated anxiety and depression profile (3) Serious anxiety and depression profile, suggesting two groups of susceptible animals with different intensities of altered behavior. Also, fluoxetine could change the ratio of rats previously classified in groups 2 or 3, showing the beneficial effects of antidepressant treatment. Our results demonstrate that CUSB has different consequences even in subjects that experienced the same stress protocol. Also, fluoxetine has different efficacy in recovering behavior associated with the age of exposure to stress. Finally, we suggest k-means as an easy and useful method to apply in susceptible rodent studies of depression and to study the individual efficacy of antidepressant treatment.
生活中的慢性应激被认为是人类发生精神疾病的一个风险因素。慢性不可预测应激程序（CUSB）是一种通过对啮齿动物施加应激来研究抑郁症的动物模型。CUSB可诱导抑郁和焦虑行为指标，这些指标可通过抗抑郁药物氟西汀进行调节。然而，众所周知，并非所有个体都会出现类似抑郁的行为，或者对抗抑郁治疗无反应。在抑郁模型中，筛选这些个体在应激易感性或抗抑郁治疗疗效方面差异的方法尚未得到充分研究。在此，我们表明糖精消耗量、不动时间以及在区域中心停留的时间可作为筛选应激和抑郁易感性的行为指标，我们还表明氟西汀治疗的疗效因应激发生时的年龄而异。首先，我们发现经过CUSB（在青春期、成年期或两个时期）后，啮齿动物表现出抑郁和焦虑特征。其次，我们发现氟西汀（10mg/kg）可使所有应激组的抑郁症状得到缓解，但不能缓解焦虑症状。最后，我们使用机器学习聚类方法（k均值），根据应激暴露和抗抑郁治疗所调节的个体效应，对所有组的个体进行分类，以找出应激效应与药理疗效的比例。以行为改变作为分类指标，我们发现了三个可能的聚类，（1）无改变，（2）中度焦虑和抑郁特征，（3）严重焦虑和抑郁特征，这表明存在两组行为改变强度不同的易感动物。此外，氟西汀可改变先前分类为第2组或第3组大鼠的比例，显示出抗抑郁治疗的有益效果。我们的结果表明，即使在经历相同应激程序的个体中，CUSB也会产生不同的后果。此外，氟西汀在恢复与应激暴露年龄相关的行为方面具有不同的疗效。最后，我们建议k均值作为一种简单且有用的方法，可应用于易感啮齿动物的抑郁症研究以及研究抗抑郁治疗的个体疗效。
