用小鼠训练和社会观察教老鼠主动改变笼子
Özet
本协议介绍了一种通过发声训练对大鼠进行笼型改变的方法。大鼠不仅通过直接训练, 而且通过观察性学习来学习所期望的行为。实施这一快速而简单的协议可能有助于改善啮齿动物设施的福祉和卫生。
Abstract
笼式清洗是一种常规执行的畜牧程序, 已知在实验大鼠中诱发压力。由于压力会对幸福产生负面影响, 并可能影响研究结果的可比性和重现力, 因此应尽量减少和避免实验动物所承受的压力。此外, 大鼠和动物看守人在笼中的直接接触会造成卫生风险, 因此可能对大鼠的福祉和研究的质量产生负面影响。
我们的协议旨在改进常规执行的笼型更换程序。为此, 我们提出了一个可行的协议, 使大鼠通过发声训练和观察, 自愿地改变到一个干净的笼子学习。这项培训有助于减少因身体紊乱和与笼子变化有关的处理而引起的压力, 同时可以减少动物和动物看管者在训练阶段完成后的直接接触。
对大鼠进行点对中训练的实现是快速而简单的。大鼠通常对训练感兴趣, 并有效地学习所需的行为, 这就需要通过管子改变笼子。即使没有训练, 老鼠也学会通过观察来执行所期望的行为, 因为80% 的观察学习小组在测试时成功地改变了笼子。培训进一步有助于建立一个教练和动物之间的信任关系。由于卫生和福祉在动物实验中都非常重要, 本议定书也可能有助于改进高质量的研究。
Introduction
常规程序可能导致实验室动物的压力1,2,3,4。结果表明, 笼型改变确实增加了4、5、6大鼠的心血管参数和一般活动。这种压力反应至少可以部分归结于与笼型变化过程相关的物理干扰和处理, 而不是新的陌生环境2,4。特别重要的是压力对被视为动物的福祉的负面影响7。此外, 压力还会诱发行为和其他身体参数的变化, 包括自主神经系统、神经内分泌系统和免疫系统。因此, 压力通常被称为在动物实验中出现意外偏差的可能来源, 应尽量避免在高质量的动物研究7,8。减少实验动物压力的一种方法是训练。训练动物通常是一个非常有用的工具, 实验室动物管理, 事实上, 要求欧盟指令 2010/63/欧盟9。训练可以作为一种充实的形式, 有助于为实验准备动物;因此, 培训有助于维持和提高实验室设置10、11、12的福祉。一种可能的训练方法是正强化训练 (PRT)。PRT 是一种操作性条件反射调节的形式, 奖励 (例如,食物奖励) 与所需行为13联系在一起。这种形式的训练已经在非人类灵长类动物的实验室设置中普遍使用, 以减轻压力并增进福祉, 并在其他各种动物物种10、13中得到普及, 14,15,16。自愿运动培训也经常用于畜牧业管理17、18、19。PRT 不仅是与动物合作的有用工具;它同样有利于动物的福祉, 无论训练的行为是否直接使用20。这里所描述的正强化训练协议旨在通过给予鼠自愿参与程序的机会, 避免在例行执行笼式改变期间出现任何形式的压力。
除了对动物可能造成的压力外, 动物设施的工作流程始终为维持卫生状况提供了陷阱, 特别是在实验室动物和动物照料者之间的直接接触有卫生风险的情况下污染。在专门从事啮齿动物的动物设施中, 将动物从脏物转移到干净的笼子里, 可以提供经常性和高工作量。此程序通常包括动物和人类之间的直接接触, 因此代表一个卫生风险因素, 由于可能转移的病原体在人类皮肤上定居21。除了从其他动物载体转移, 致病和非致病生物侵入动物设施最频繁地通过人类22,23。由于减少的健康与减少的福祉相关, 甚至亚临床感染可能是 nonreproducible 实验结果的原因, 这应该清楚地避免24,25。在这个帐户上, 训练动物到自愿改变笼子进一步使笼的传导变化在训练后几乎没有任何直接接触动物和动物看守, 从而降低了潜在的卫生风险, 同时执行实验程序。
我们训练大鼠主动更换网箱的协议, 可以作为实验室大鼠管理的一个有用工具, 它将训练作为一种认知充实的形式与日常工作的表现联系起来。因此, 我们的议定书是一种动物友好的程序, 有助于提高实验动物设施中大鼠的福祉。由于笼子在训练阶段可以在动物和动物看守者之间几乎没有任何直接接触的条件下进行改变, 它可能还有助于保持高水平的卫生水平, 从而进一步改善动物研究。
Protocol
Representative Results
Discussion
上文所述的协议是我们以前描述的用于实验室小鼠的10号训练方案的一个有用的扩展应用。该实施只需要每天几分钟, 总共七周, 包括驯化, 习惯和唱歌训练。为了可行性, 本协议仅限于每周几周, 每对老鼠的会话时间约为十分钟。该协议在大型大鼠群体中的建立是很耗时的, 但如果动物被指定为长期试验或育种者, 它可以帮助改善笼子长期变化的过程。此外, 在进行实验时减少干扰?…
Açıklamalar
The authors have nothing to disclose.
Acknowledgements
作者非常感谢托马斯. 瓦克的技术支持。我们进一步感谢海林博士对她的亲切支持。
Materials
| Target Stick with Clicker | Trixie | 2282 | |
| Metal Pipe (Alu Flexrohr nw 100) | Rotheigner | available in construction marktes | |
| White Chocolate/ white chocolate cream | Company doesn't matter, preferable organic quality | ||
| Prism Version 6.0 for Mac | GraphPad Software |
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