Development and validation of an automated test of animal affect and welfare for laboratory rodents

实验室啮齿动物动物影响和福利自动测试的开发和验证

• 批准号: NC/K00008X/1
• 负责人: Michael Mendl
• 金额: $ 43.03万
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FK00008X%2F1
• 关键词: Development; validation; automated; test; animal

A central goal of NC3Rs is the refinement of laboratory procedures to minimise animal pain, suffering, and lasting harm, and to improve laboratory animal welfare. To achieve this, it is essential that we use scientifically validated measures to quantify how experimental, housing, and husbandry procedures affect welfare, and whether refinements do indeed lead to improvements. NC3Rs have therefore called for research to develop new and better welfare measures. Our project will provide such a measure to better assess the welfare of rats and mice (81% of laboratory animals used in the UK in 2010).The assumption that non-human animals can subjectively experience negative emotional (affective) states and hence suffer underpins concerns for animal welfare. Affective state is thus a key determinant of an animal's welfare. However, because subjective experiences are essentially private, and cannot be measured directly, we need to identify indicators that indirectly reflect an animal's affective state. For example, we can measure physiological changes, such as hormone levels, or behavioural indicators, such as an animal's behaviour in an unprotected open space. However, whilst valuable, such indicators have important limitations which a more recent approach that we have developed seeks to address. Human psychological studies show that, when feeling happier, people are more likely to judge an ambiguous event as having a positive outcome than when they are feeling down; their proverbial glass is half-full. If the same is true of other animals, then by measuring the judgements they make in ambiguous situations, we may gain useful information about how they are feeling too. To explore this possibility, we have developed a novel, non-verbal test of 'judgement bias' underpinned by theoretical models of decision-making. The test allows us to systematically investigate whether animals judge an ambiguous stimulus positively ('optimistic') or negatively ('pessimistic'). Recent studies of rats, sheep, dogs, monkeys, and starlings support the hypothesis that animals in a more positive affective state do indeed show a more 'optimistic' response to ambiguous stimuli, indicating that this technique may be a very good way of assessing emotional state in animals.However, existing judgement bias tests are relatively time-consuming, involving hands-on training of animals, and no methods have been developed for mice, the most widely used laboratory species. Therefore, we will develop an automated version of our judgement bias test that can be used for laboratory rodents, including mice. We will then validate this new test by employing a range of carefully-selected pharmacological and environmental treatments, each designed to induce a particular, transient change in affective state. By examining how treatments affect the size of the responses shown, we will be able to see whether the method can quantify the intensity of an emotional state. We will also compare enriched and standard housing conditions, and other determinants of long-term emotional state, to see whether the test can detect the cumulative effects of long-term experience on affect. 'Cumulative suffering' is hard to measure, yet vitally important for an animal's lifetime welfare, and we anticipate that our approach can provide a good indication of this state. An industrial partner has expressed interest in further implementing the test that we develop for widespread use, for example by incorporating it into a home-cage testing system.The study will also produce computational models of how affective states change in response to external events. These may provide the basis for modelling the effects of experimental treatments on an animal's affective state, hence facilitating better and more humane planning of studies. We hope that this project will lay the foundations for further development of such models.

NC3R 的核心目标是完善实验室程序，以最大程度地减少动物疼痛、痛苦和持久伤害，并改善实验动物福利。为了实现这一目标，我们必须使用经过科学验证的措施来量化实验、住房和饲养程序如何影响福利，以及改进是否确实会带来改善。因此，NC3R 呼吁进行研究以制定新的、更好的福利措施。我们的项目将提供这样一种措施，以更好地评估大鼠和小鼠的福利（2010 年英国使用了 81% 的实验动物）。非人类动物可以主观地经历负面情绪（情感）状态并因此遭受痛苦的假设是基础对动物福利的担忧。因此，情感状态是动物福利的关键决定因素。然而，由于主观体验本质上是私人的，无法直接测量，因此我们需要确定间接反映动物情感状态的指标。例如，我们可以测量生理变化，例如激素水平，或行为指标，例如动物在不受保护的开放空间中的行为。然而，这些指标虽然有价值，但也有重要的局限性，我们开发的最新方法试图解决这些局限性。人类心理学研究表明，当人们感到快乐时，与情绪低落时相比，人们更有可能将模糊的事件判断为具有积极的结果；众所周知，他们的杯子是半满的。如果其他动物也是如此，那么通过测量它们在模棱两可的情况下做出的判断，我们也可能获得有关它们感受的有用信息。为了探索这种可能性，我们开发了一种新颖的、非语言的“判断偏差”测试，以决策理论模型为基础。该测试使我们能够系统地研究动物对模糊刺激的判断是积极的（“乐观”）还是消极​​的（“悲观”）。最近对老鼠、绵羊、狗、猴子和椋鸟的研究支持了这样的假设：处于更积极情感状态的动物确实对模糊刺激表现出更“乐观”的反应，这表明这种技术可能是评估情绪的一种非常好的方法。然而，现有的判断偏差测试相对耗时，涉及对动物的实际训练，并且尚未开发出针对小鼠这种最广泛使用的实验室物种的方法。因此，我们将开发一个自动化版本的判断偏差测试，可用于实验室啮齿动物，包括小鼠。然后，我们将通过采用一系列精心挑选的药理学和环境治疗来验证这项新测试，每种治疗都旨在诱导情感状态的特定、短暂的变化。通过检查治疗如何影响所显示的反应的大小，我们将能够了解该方法是否可以量化情绪状态的强度。我们还将比较丰富的和标准的住房条件，以及长期情绪状态的其他决定因素，看看测试是否可以检测长期经历对情感的累积影响。 “累积痛苦”很难衡量，但对于动物的一生福利至关重要，我们预计我们的方法可以很好地表明这种状态。一位工业合作伙伴表示有兴趣进一步实施我们开发的广泛使用的测试，例如将其纳入家庭笼式测试系统中。该研究还将产生情感状态如何响应外部事件而变化的计算模型。这些可以为模拟实验治疗对动物情感状态的影响提供基础，从而促进更好、更人性化的研究规划。我们希望这个项目能为此类模型的进一步发展奠定基础。