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.

NC 3R的核心目标是完善实验室程序，以最大限度地减少动物疼痛，痛苦和持久伤害，并改善实验室动物福利。为了实现这一目标，我们必须使用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，以及改进是否确实导致改善。因此，第三次国家信息通报呼吁开展研究，制定新的和更好的福利措施。我们的项目将提供这样一个措施，以更好地评估大鼠和小鼠的福利（81%的实验室动物在2010年在英国使用）。假设非人类动物可以主观地经历负面的情绪（情感）状态，因此遭受支持动物福利的关注。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，不能直接测量，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，如激素水平，或行为指标，如动物在无保护的开放空间中的行为。然而，虽然这些指标很有价值，但也有重要的局限性，我们最近制定的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，他们更有可能将一个模棱两可的事件判断为有积极的结果，而不是当他们感到沮丧时;他们的谚语是半杯水满。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，我们也可以获得关于它们感受的有用信息。为了探索这种可能性，我们开发了一种新的，非语言的测试“判断偏差”的决策理论模型的基础上。该测试允许我们系统地研究动物是否积极（“乐观”）或消极（“悲观”）地判断模糊的刺激。最近对大鼠、绵羊、狗、猴子和椋鸟的研究支持了这样一个假设，即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动物情感状态的一种非常好的方法。然而，现有的判断偏差测试相对耗时，涉及对动物的动手训练，并且还没有开发出用于小鼠的方法，小鼠是最广泛使用的实验室物种。因此，我们将开发一种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选择的药理学和环境治疗来验证这种新的测试，每种治疗都旨在诱导情感状态的特定短暂变化。通过研究治疗如何影响所显示的反应的大小，我们将能够看到该方法是否可以量化情绪状态的强度。我们还将比较丰富和标准的住房条件，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验对情绪的累积影响。“累积的痛苦”很难衡量，但对动物的终身福利至关重要，我们预计我们的方法可以很好地指示这种状态。一个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测试系统。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，从而促进更好和更人性化的研究计划。我们希望，这一项目将为进一步发展这种模式奠定基础。