Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North West-University, Potchefstroom, South Africa.
MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
Curr Med Chem. 2018;25(41):5662-5689. doi: 10.2174/0929867324666170523125256.
Obsessive-compulsive disorder is a heterogeneous and debilitating condition, characterized by intrusive thoughts and compulsive repetition. Animal models of OCD are important tools that have the potential to contribute significantly to our understanding of the condition. Although there is consensus that pre-clinical models are valuable in elucidating the underlying neurobiology in psychiatric disorders, the current paper attempts to prompt ideas on how interpretation of animal behavior can be expanded upon to more effectively converge with the human disorder. Successful outcomes in psychopharmacology involve rational design and synthesis of novel compounds and their testing in well-designed animal models. As part of a special journal issue on OCD, this paper will 1) review the psychobehavioral aspects of OCD that are of importance on how the above ideas can be articulated, 2) briefly elaborate on general issues that are important for the development of animal models of OCD, with a particular focus on the role and importance of context, 3) propose why translational progress may often be less than ideal, 4) highlight some of the significant contributions afforded by animal models to advance understanding, and 5) conclude by identifying novel behavioral constructs for future investigations that may contribute to the face, predictive and construct validity of OCD animal models. We base these targets on an integrative approach to face and construct validity, and note that the issue of treatment-resistance in the clinical context should receive attention in current animal models of OCD.
强迫症是一种异质且使人虚弱的疾病，其特征是存在侵入性思维和强迫性重复。强迫症的动物模型是重要的工具，它们有可能对我们对该疾病的理解做出重大贡献。尽管人们一致认为，临床前模型在阐明精神疾病的潜在神经生物学方面具有价值，但本文试图提出如何扩展对动物行为的解释，以更有效地与人类疾病相吻合。精神药理学的成功结果涉及新型化合物的合理设计和合成，以及在精心设计的动物模型中的测试。作为 OCD 特刊的一部分，本文将 1）回顾 OCD 的心理行为方面，这些方面对于如何阐述上述观点很重要，2）简要阐述发展 OCD 动物模型的一般问题，特别关注背景的作用和重要性，3）提出为什么转化进展可能并不理想，4）突出动物模型在推进理解方面的一些重要贡献，5）最后确定未来研究的新行为结构，这些结构可能有助于 OCD 动物模型的表面、预测和结构有效性。我们基于一种综合方法来考虑表面和结构有效性，并指出在 OCD 的临床环境中，治疗抵抗的问题应该得到关注。
