Validating inactivity in the home-cage as a depression-like state indicator in mice

验证家笼中的不活动作为小鼠抑郁状态的指标

• 批准号: BB/P019218/1
• 负责人: Michael Mendl
• 金额: $ 56.11万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP019218%2F1
• 关键词: Validating; inactivity; home; cage; depression

Non-human animals (hereafter animals) can become strangely inactive in their home pens, being motionless (although awake) and not interacting with their environment. The affective states associated with this waking inactivity are, however, still not well understood. Compellingly, reduced activity and lack of engagement with the environment is one phenomenon supporting clinical depression diagnosis in humans. Moreover, the aetiology of human depression emphasizes aversive life events and chronic stress as common triggers of the disorder, and animals showing waking inactivity have often experienced an array of stressors, such as living in socially and/or spatially restricted environments. We therefore propose that,in animals, specific forms of waking inactivity characterised by being immobile with eyes open represent a marker of depression-like conditions.This project builds upon our research that has already delineated in mice Mus musculus a specific form of waking inactivity [being awake but motionless within the home cage], triggered by relatively barren lab cages and associated with a key depression-like symptom of the human illness: the tendency to give up when faced with challenge. Our goal is to further test the hypothesis that waking inactivity is a spontaneous depression-like symptom in mice, which would be an easily measured home-cage indicator of animal welfare that could be translated across species. To achieve this goal, we will adopt a translational 'from humans to animals' approach, using depressed people as a 'model' for inactive mice. As such, potential markers of animal depression-like conditions are expected to co-vary with a range of symptoms in animals similar to those described in human depression. Moreover, for an animal condition to be deemed homologous to a human illness, the processes by which both animal and humans fall into, and are released from, this state must share similarities. If waking inactivity reflects depression-like states in mice, its risk and curative factors should thus be similar to those of the human disease. Our investigations will thus broadly target shared aetiology [is waking inactivity triggered by a combination of risk factors triggering clinical depression in humans?], symptomatic similarities [does waking inactivity co-vary with a range of symptoms similar to those of clinical depression in humans?], and common curative factors [is waking inactivity alleviated by treatments clinically efficient in humans?]. Cognitive symptoms are a frequent part of depression in humans. A quick and easy cognitive measure of depression-like states is however needed in animals, and we will thus first validate such a measure of in mice, and then use this later to assess the symptomatic similarities between waking inactivity in mice and depression in humans.If confirmed, our results will validate in-cage waking inactivity as a marker of a depression-like condition in mice. This has clear implications for animal welfare, as validated methods of identifying states of mental suffering are first required if we are to detect welfare problems in situ, assess the effectiveness of refinements, and maximise the welfare of lab animals. The ability to detect depression-like states also has crucial implications from a research perspective, since mice in negative affective states may for instance represent improved models of human depression, while potentially invalidating research where stress and depression are not of interest. A new, non-invasive tool to measure affective states will thus be of interest to animal welfare scientists, neuroscientists & psychopharmacologists interested in the assessment of animal affect; biomedical scientists whose research may be impacted by spontaneous occurrence of depression-like states in their subject animals; and laboratory managers & scientists seeking to improve welfare of their research animals.

非人类动物（以下简称动物）在它们的围栏中可能会变得奇怪地不活跃，一动不动（尽管醒着）并且不与环境互动。然而，与这种清醒时不活动相关的情感状态仍然没有得到很好的理解。令人信服的是，活动减少和缺乏与环境的接触是支持人类临床抑郁症诊断的一种现象。此外，人类抑郁症的病因学强调厌恶的生活事件和慢性压力是这种疾病的常见诱因，而表现出清醒时不活动的动物经常经历一系列压力源，例如生活在社会和/或空间受限的环境中。因此，我们提出，在动物中，以睁着眼睛一动不动为特征的特定形式的清醒不活动代表了类似抑郁症的标志。该项目建立在我们的研究基础上，该研究已经在小鼠小家鼠中描述了一种特定形式的清醒不活动[在家里的笼子里保持清醒但一动不动]，这是由相对贫瘠的实验室笼子引发的，并与人类疾病的一种类似抑郁症的关键症状有关：面对挑战时倾向于放弃。我们的目标是进一步检验这样的假设：醒来时不活动是小鼠自发的类似抑郁症的症状，这将是一个易于测量的动物福利的家笼指标，可以跨物种转化。为了实现这一目标，我们将采用“从人类到动物”的转化方法，使用抑郁的人作为不活跃小鼠的“模型”。因此，动物类抑郁症的潜在标志物预计会与动物中类似于人类抑郁症所描述的一系列症状共同变化。此外，为了使动物的病症与人类的疾病同源，动物和人类陷入和摆脱这种状态的过程必须具有相似之处。如果醒来时不活动反映了小鼠的抑郁样状态，那么其风险和治疗因素应该与人类疾病相似。因此，我们的研究将广泛针对共同的病因学[醒来不活动是否是由引发人类临床抑郁症的风险因素组合引发的？]、症状相似性[醒来不活动是否与一系列与人类临床抑郁症相似的症状共同变化？ ]，以及常见的治疗因素[临床上对人类有效的治疗是否可以减轻清醒时的不活动？]。认知症状是人类抑郁症的常见组成部分。然而，动物需要一种快速、简单的抑郁样状态认知测量方法，因此我们将首先在小鼠中验证这种测量方法，然后用它来评估小鼠清醒时不活动和人类抑郁症之间症状的相似性。如果得到证实，我们的结果将验证笼内清醒不活动作为小鼠抑郁症样病症的标志。这对动物福利具有明显的影响，因为如果我们要现场检测福利问题、评估改进的有效性并最大限度地提高实验动物的福利，首先需要确定精神痛苦状态的有效方法。从研究的角度来看，检测类似抑郁状态的能力也具有重要意义，因为处于负面情感状态的小鼠可能代表人类抑郁症的改进模型，同时可能使压力和抑郁症不感兴趣的研究无效。因此，对动物情感评估感兴趣的动物福利科学家、神经科学家和精神药理学家将对一种新的、非侵入性的情感状态测量工具感兴趣；生物医学科学家，其研究可能会受到研究对象动物自发发生的抑郁样状态的影响；以及寻求改善研究动物福利的实验室管理人员和科学家。

项目成果

Animal affect and decision-making.

动物的影响和决策。

• DOI: http://dx.10.1016/j.neubiorev.2020.01.025
• 发表时间: 2020
• 期刊: Neuroscience and biobehavioral reviews
• 影响因子: 8.2
• 作者: Mendl M

Do greater levels of in-cage waking inactivity in laboratory mice reflect a spontaneous depression-like symptom? A pharmacological investigation.

实验室小鼠在笼中醒来时不活动的程度较高是否反映了自发的抑郁样症状？

• DOI: http://dx.10.1016/j.pbb.2021.173311
• 发表时间: 2022
• 期刊: Pharmacology, biochemistry, and behavior
• 作者: Fureix C

Validating greater 'Inactive But Awake' behaviour in the home-cage as a depression-like state indicator in mice.

验证家笼中更大的“不活动但清醒”行为作为小鼠抑郁状态的指标。

• 发表时间: 2021
• 作者: Fureix C

Inactive but awake behaviour as a potential indicator of a housing-induced depressive-like state in mice

不活跃但清醒的行为是小鼠住房诱导的抑郁样状态的潜在指标

• 发表时间: 2019
• 作者: Finnegan E

Can animals develop depression? An overview and assessment of 'depression-like' states

动物会患上抑郁症吗？

• DOI: http://dx.10.1163/1568539x-bja10132
• 发表时间: 2021
• 期刊: Behaviour
• 影响因子: 1.3
• 作者: MacLellan A