Crombag Hans S, Duka Theodora, Stephens David N
School of Psychology and Sussex Neuroscience, The University of Sussex, Brighton, UK.
Curr Top Behav Neurosci. 2025;72:551-594. doi: 10.1007/7854_2024_485.
The use of animal models continues to be essential for carrying out research into clinical phenomena, including addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate, and this may go some way to account for the apparent failures of discoveries from animal models, including the identification of potential novel therapies, to translate to the clinic. We argue here that it is overambitious and misguided in the first place to attempt to model complex, multifacetted human disorders such as addiction in animals, and especially in rodents, and that all too frequently "validity" of such models is limited to superficial similarities, referred to as "face validity", that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, a more profitable approach is to identify (a) well-defined intermediate human behavioural phenotypes that reflect defined, limited aspects of, or contributors to, the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioural phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of past and continuing weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.
动物模型的使用对于开展包括成瘾在内的临床现象研究仍然至关重要。然而,临床病症的复杂性不可避免地意味着,即便最佳的动物模型也存在不足,这或许在一定程度上解释了动物模型研究成果(包括潜在新疗法的识别)在转化至临床时明显失败的原因。我们在此认为,首先试图在动物尤其是啮齿动物身上模拟诸如成瘾这种复杂、多方面的人类疾病是野心勃勃且误入歧途的,而且此类模型的“有效性”常常仅限于表面相似性,即所谓的“表面效度”,这种表面效度反映的是与临床情况截然不同的潜在现象和生物学过程。相反,一种更有成效的方法是识别:(a)明确界定的中间人类行为表型,这些表型反映人类临床疾病的特定、有限方面或促成因素;(b)开发在心理过程和潜在神经生物学机制方面与那些离散的人类行为表型同源的动物模型。文中列举了过去和当前存在的弱点示例,并提出了一些更有限的方法建议,这些方法可能使实验动物与人类状况之间具有更好的同源性。