Program 'Emotion and Cognition', Department of Farm Animal Health, Veterinary Faculty, Utrecht University, PO Box 80166, 3508 TD Utrecht, the Netherlands.
Behav Brain Funct. 2009 Feb 25;5:11. doi: 10.1186/1744-9081-5-11.
Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration.Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended) replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result.Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia.In a manner congruent to that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s) of a model and by defining better evaluation criteria, based on the proposed use of the model.
动物模型在所有生物医学研究领域中都起着核心作用。尽管在研究神经精神障碍和行为功能障碍时已经使用动物模型很长时间了，但动物模型的构建、开发和评估过程很少被系统地涉及。本文提出了一种开发动物模型和评估其质量的迭代、多阶段的轨迹。该过程始于定义模型的目的（多个），优先基于关于脑-行为关系的假设。然后，开发和测试模型。模型的评估考虑了科学和伦理标准。模型开发需要多学科的方法。临床前和临床专家应建立一套科学标准，模型必须符合这些标准。科学评估包括评估模型的可重复性/可靠性、预测性、构建性和外部有效性/可推广性以及相关性。我们强调在验证过程中（系统和扩展）重复的作用。可以应用多层次的“重复电池”来估计模型的可靠性/可重复性、有效性和可推广性。
在动物的许多缺陷模型中，动物福利受到损害是固有的。不幸的是，“动物福利”是一个定义模糊的概念，难以建立确切的评估标准。在模型构建和评估过程的任何阶段，都必须权衡动物的福利以及是否有必要采取行动来减轻不适，同时进行科学评估。如果模型不符合预设的科学标准，或者动物福利受到严重损害，则应停止使用该模型。使用新生海马损伤大鼠作为精神分裂症模型的应用示例说明了评估程序的应用。
通过应用本文所阐述的程序，并以改进动物模型为指导，通过仔细定义模型的目的以及根据模型的预期用途定义更好的评估标准，可以改进模型的开发和评估过程本身。
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