Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology.
Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology.
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DOI：
10.1016/j.neuroscience.2016.09.012
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发表时间：
2017-03-14
期刊：
影响因子：
3.3
通讯作者：
Veenstra-VanderWeele J
中科院分区：
文献类型：
--
作者：
Zike I;Xu T;Hong N;Veenstra-VanderWeele J
强迫症（OCD）是一种常见的神经精神疾病，其分子基础尚不清楚。遗传和非遗传风险因素的识别在很大程度上是难以捉摸的，主要是因为缺乏动力。相比之下，神经影像学一直表明皮质-纹状体-丘脑-皮质（CSTC）回路与强迫症有关。药物治疗研究也显示出特异性，强迫症症状对长期使用血清素再摄取抑制剂的治疗有一致的反应；尽管大多数患者都留下了残余损伤。理论上，动物模型可以提供从神经影像和药理学数据到细胞和分子水平的病理生理学理解的桥梁。已经使用遗传、免疫学、药理学和光遗传学工具提出了几种小鼠模型。这些实验模型系统可以测试有关强迫行为起源的假设。一些模型已经产生了类似强迫性的行为，特别是过度梳理毛发，并且一些模型已经表现出对慢性血清素再摄取抑制剂的反应，建立了面部有效性和预测有效性。在对强迫症风险因素了解有限的情况下，构建效度更难建立。我们当前的模型可以帮助我们剖析可以在啮齿类动物中引发强迫症相关行为的回路和分子途径。我们希望，这种不断加深的理解，加上不断发展的技术，能够让我们在更好地理解强迫症风险因素时做好准备。
Obsessive Compulsive Disorder (OCD) is a common neuropsychiatric disorder with unknown molecular underpinnings. Identification of genetic and non-genetic risk factors has largely been elusive, primarily because of a lack of power. In contrast, neuroimaging has consistently implicated the cortico-striatal-thalamo-cortical (CSTC) circuits in OCD. Pharmacological treatment studies also show specificity, with consistent response of OCD symptoms to chronic treatment with serotonin reuptake inhibitors; although most patients are left with residual impairment. In theory, animal models could provide a bridge from the neuroimaging and pharmacology data to an understanding of pathophysiology at the cellular and molecular level. Several mouse models have been proposed using genetic, immunological, pharmacological, and optogenetic tools. These experimental model systems allow testing of hypotheses about the origins of compulsive behavior. Several models have generated behavior that appears compulsive-like, particularly excessive grooming, and some have demonstrated response to chronic serotonin reuptake inhibitors, establishing both face validity and predictive validity. Construct validity is more difficult to establish in the context of a limited understanding of OCD risk factors. Our current models may help us to dissect the circuits and molecular pathways that can elicit OCD-relevant behavior in rodents. We can hope that this growing understanding, coupled with developing technology, will prepare us when robust OCD risk factors are better understood.