Could Ultrasonic Vocalisations Provide The Elusive, Graded Measure Of Affective State Needed To Inform Refinements For The Laboratory Rat?

动物研究要求研究考虑3R（减少，优化和替换）。改良涉及使用对动物造成最小痛苦的方法，这可能更难以客观评估。为了达到细化要求的能力，量化动物的情感或“情感”的经验。虽然动物行为的明显变化可以提供一些信息，但这些信息并不能提供足够的敏感性来理解情感影响。我们的研究开创了测量动物情感状态的客观方法的发展。通过翻译人类心理学的行为方法，我们开发并验证了新的测定方法，可以准确测量动物对不同干预措施的积极或消极情感体验。我们使用了其中的一种实验，即情感偏差测试，来证明老鼠发出的高频叫声可以对它们的个体情感体验进行分级测量。这提出了令人兴奋的可能性，测量这些超声波发声可能提供一个简单易用的方法来评估改进。我们的方法不需要昂贵的设备或专业知识，这意味着它可以很容易地在任何动物研究设施中设置和使用。以前的研究表明，成年大鼠在经历假定的积极或消极事件时，分别发出50 kHz或22 kHz的叫声。虽然间接的证据来支持这一想法已经实现，我们以前没有一个可靠的客观的方法来准确地量化这些电话和动物的个人情感体验之间的关系。到目前为止，这些超声波发声和情感状态之间的直接相关性只在大鼠中进行了与人类模拟游戏或“挠痒痒”相关的测试。情感偏见测试是一个简单的，奖励为基础的任务，我们已经证明，可以提供一个分级的措施，在急性心理或药物干预的大鼠的情感状态。该任务测量与联想学习和记忆相关的情感偏差。情感偏差描述了情绪状态对不同认知过程的影响，并且已知其调节人类和非人类动物的学习和记忆以及决策行为。认知可能偏向于积极或消极的方向，受到情绪状态的短期变化和类似情绪的核心影响变化的影响。使用我们的情感偏见测试，我们将测试的假设，超声波发声可以提供一个同样敏感的措施，动物的情感状态，但使用的方法，可以广泛采用整个科学界。我们的研究将电话与我们在ABT中测量的积极或消极情感状态相关联，这将为该方法的有效性提供直接证据。我们还将测试一组处于假定的抑郁样状态的动物，我们发现负面情感偏见是增强的。我们的目的是确定发声是否也发生了类似的改变，从而提供一种理解动物核心情感状态的方法。这些验证研究将告诉我们，记录动物的叫声是否可以提供有关它们在急性体验期间以及与核心情感或“情绪”有关的情绪状态的信息。在我们的最终工作包中，我们将把方法转化为在家庭笼中以及在个体和群体水平上对实验室常用的操作做出响应的测试。我们还将测试两种改进方法，一种是人类处理习惯，另一种是一种新型的笼子系统，旨在增加空间和社会互动，同时也适用于处理。该项目的成果将是使更多的研究人员能够研究改进的方法，并使机构能够使用简单，非侵入性和非专业的方法监测其殖民地的情感状态。

Animal research requires that studies consider the 3Rs (Reduce, Refine and Replace). Refinement involves using methods which cause the least suffering to the animal, and this can be more challenging to assess objectively. To achieve refinement requires the ability to quantify the animals affective or 'emotional' experience. Although overt changes in the animal's behaviour can provide some information, these do not offer sufficient sensitivity to understand the emotional impacts. Our research has pioneered the development of objective methods to measure animals' affective state. By translating behavioural methods from human psychology, we have developed and validated novel assays which accurately measure animals positive or negative affective experience of different interventions. We have used one of these assays, the affective bias test, to demonstrate that high frequency calls emitted by rats provide a graded measure of their individual emotional experience. This raises the exciting possibility that measuring these ultrasonic vocalisations may provide a simple and easy to use method to evaluate refinements. Our approach will not require costly equipment or specialist expertise meaning it could be readily set-up and utilised within any animal research facility.Previous studies suggest that adult rats emit 50kHz or 22kHz calls when they experience putative positive or negative events, respectively. Although indirect evidence to support this idea has been achieved, we have not previously had a reliably objective method to accurately quantify the relationship between these calls and the animal's individual affective experience. Direct correlation between these ultrasonic vocalisations and affective state has so far only been tested in relation to human simulated play or 'tickling' in rats. The affective bias test is a simple, reward-based task which we have shown can provide a graded measure of the affective state of rats during acute psychosocial or pharmacological interventions. The task measures affective biases related to associative learning and memory. Affective bias describes the effect of emotional state on different cognitive processes and are known to modulate learning and memory and decision-making behaviour in human and non-human animals. Cognition can be biased in either a positive or negative direction influenced by both short-term changes in emotional state and arising from changes in core affect akin to mood. Using our affective bias test, we will test the hypothesis that ultrasonic vocalisations can provide an equally sensitive measure of animal's affective state but using a method which can be widely adopted across the scientific community. Our studies correlating calls with our measure of positive or negative affective state in the ABT will provide direct evidence of the validity of the approach. We will also test a cohort of animals in a putative depression-like state where we have found that negative affective biases are potentiated. Our aim is to establish whether vocalisations are similarly altered and hence provide a way of understanding animals core affective state. These validation studies will tell us whether recording animals calls can provide information about their emotional state both during acute experiences and in relation to core affect or 'mood'. In our final work package, we will translate the approach to testing in the home-cage and at an individual and populations level in response to manipulations commonly used the laboratory. We will also test two refinement methods, habituation to human handling and a novel caging system designed to increase space and social interactions whilst also being practical for handling. The outcomes of this project will be methods to enable many more researchers to study refinement and enable institutions to monitor the affective state of their colonies using a simple, non-invasive and non-specialist method.