煽动抑郁症状，行为变化和不利健康结果鼠害一个不可预知的慢性轻度应激协议
Summary
The unpredictable chronic mild stress (UCMS) protocol is a validated method for studying behavioral and physiological changes associated with chronic stress and depressive symptoms. Eight weeks of imposition of the UCMS protocol induces behavioral changes and poor health outcomes in rodents of either gender.
Abstract
慢性，未解决的压力是临床抑郁症的发展的一个主要危险因素。而应激抑郁的许多临床前模型已报道，在不可预测的慢性应激（UCMS）协议是用于诱导行为症状通常与临床抑郁症有关，如快感缺乏，改变的梳理行为建立翻译相关的模型，和习得性无助在啮齿类动物。该UCMS协议也引起生理（E·G。，hypercortisolemia，高血压）和神经系统（ 例如 ，快感缺乏，习得性无助感），其在临床上与抑郁症相关的变化。重要的是，UCMS引起的抑郁症状可以通过长期得到改善，但不严重，治疗常见的SSRIs类药物。这样，UCMS协议提供了许多优点急性应激协议或，利用更极端的压力源协议。我们的协议包括随机，每天暴露于7不同的STREssors：潮湿的床上用品，拆除床上用品，笼倾斜，改变光/暗周期，社会压力，浅水洗澡，捕食者的声音/气味。 3-4小时，每天给这些轻度压力使鼠类为8周后，我们证明这两种显著的行为改变和不良的健康后果心血管系统。这种方法允许进行深入询问慢性应激抑郁相关联，以及用于新的潜在的治疗剂或干预策略测试神经，行为和生理改变的。
Introduction
抑郁症精神疾病是目前世界公认的残疾和疾病负担的一个主要原因一种复杂的神经系统疾病。镍氢报告说，美国约12％的临床抑郁症，有两倍多的影响相对于男性1女。仅在美国，抑郁症占了数十亿美元的直接医疗费用估计有$ 193个十亿以上的间接成本（降低收入和生产力损失）2。抑郁症的症状包括快感缺乏，体重变化和睡眠周期，体力活动减少和个人卫生，绝望或内疚，和/或死亡或自杀的想法再次发生感情。在过去十年中，流行病学和临床研究已经表明，抑郁症是心血管疾病（CVD）的发病率和死亡率3的独立危险因素，并且是预测更严重的预后的心血管病症，包括的therosclerosis，高血压，心肌梗塞，冠状动脉疾病，不管明显的CVD 4之前的历史。尽管日益流行和抑郁症的不利公众健康的影响，这种疾病的病因学和相关的病理生理学是知之甚少和病症由于各种因素（例如，遗传，生物和环境组分）的异质性使得临床诊断难以定义。
有证据表明，无法解决的心理压力为显影抑郁疾病的一个主要因素，也可以是一种有效的致病因子联抑郁症和心血管疾病，部分是由于破坏和下丘脑-垂体-肾上腺轴（HPA）5,6-失调。 HPA轴的功能障碍是，已被链接到在抑郁症中观察到的行为和生理变化和几个CVD危险因素的发展的一个主要机制，包括血脂异常，肥胖症，糖尿病和7。抑郁症的多种临床前模型，已经开发了试图复制临床抑郁症的改变的HPA轴的活性特性的机制;这种模型提供了有效的手段进行调查慢性和急性应激动物相关的行为，神经系统和生理变化。的疾病的动物模型的有效性是基于模型的设计和其复述解剖学，神经生理学能力，和在人类疾病观察行为特征的病因和进展的相关性。此外，临床前对治疗的反应（如SSRIs的）应产生相似的结果的那些在临床环境观察。
应激抑郁的几种动物模型的研究，目前利用，如习得性无助，早期的生活压力，社会溃败的压力。然而，这些模型都有固有的缺点这减轻他们的翻译疗效8。在过去的几十年中，不可预知的慢性轻度应激（UCMS）协议已成为最翻译相关的车型之一是研究抑郁症的病理生理啮齿类动物9。该模型是基于长期暴露于压力破坏应激反应系统，并最终导致抑郁症的发展的基本概念。在UCMS协议，动物暴露于每天随机一系列温和的环境和社会压力的。它增强了该模型对人类的情况下的相关性的一个关键因素在于高度不可预测性和压力的不可控的，以及在其被引入的时间。此外，UCMS协议使用，而不是依赖于生命早期或积极的物理刺激只有轻微的压力。经过一段UCMS曝光，抑郁行为发展和媲美临床iCal的症状，包括反应减少到奖励（快感缺乏），改变身体活动和调查行为（无助和绝望），大衣状态恶化和改变性活动10。几乎所有的抑郁症症状可证实已经报道使用这种模型，并且研究已经证明，这些行为持续数周后应力的停止。此外，这些UCMS诱发抑郁行为可以逐渐被慢性尊敬，但不是急性的，治疗特别抗抑郁药，提示治疗改善了密切反映在人类中这些药物的临床操作和可变功效类似的神经效应11,14- 18。这里，我们报告了UCMS协议的详细描述，并描述典型行为和血管的结果在小鼠中。
Protocol
Representative Results
Discussion
Extensive clinical and epidemiological evidence has indicated that chronic stress is one of the most potent precipitating factors for depression. Repeated exposure to stressors may potentiate individual vulnerability to depression and other neuropsychiatric disorders as a consequence of the psychological and physical demands within the body that accumulate over time. The use of validated preclinical animal models offers a valuable translational tool for studying depression and comorbid diseases. Firstly, an ideal animal …
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
This study was supported by the American Heart Association (IRG 14330015, PRE 16850005, PRE 20380386, EIA 0740129N), and the National Institutes of Health (RR 2865AR; P20 RR 016477).
Materials
| Temporary animal cages with lids | n/a | n/a | Provided by your animal care facility |
| Rodent bedding | n/a | n/a | Provided by your animal care facility |
| Predator fur or urine | n/a | n/a | Provided by your animal care facility |
| Rodent cage drinking bottles | n/a | n/a | Provided by your animal care facility |
| 1000 ml graduated cylinder | variable | variable | This is optional. Any container from which a known quantiity of water can be poured will be appropriate |
| Wooden blocks cut from 2×4 | variable | variable | 8 inch sections are cut to facilitate cage tilt procedures |
| Soft paper towels | n/a | n/a | Provided by your institution |
| Small spray bottle | Walmart | n/a | 100-200 ml volume is sufficient, used for sucrose splash test |
| Medium (mice) or large (rats) plastic tubs for swim testing | Walmart | variable | Should be of sufficient depth that the animals cannot touch bottom (e.g., 2 feet) |
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