Witkin Jeffrey M
Psychiatric Drug Discovery, Neuroscience Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Curr Protoc Neurosci. 2008 Oct;Chapter 9:Unit 9.30. doi: 10.1002/0471142301.ns0930s45.
Obsessive-compulsive disorder (OCD) occurs with high prevalence, and the drugs used to treat OCD are limited in efficacy and have side-effect issues. The discovery of improved medicines for OCD has been hampered in part by the lack of predictive in vivo models. This unit provides a brief overview of two methods that might have such predictive utility. Marble burying and nestlet shredding are two behaviors that occur spontaneously with high frequency and repetitiveness in mice. These acute in vivo assays are relatively easy to conduct. Selective serotonin uptake inhibitors decrease these behaviors without producing motor side effects, as assessed by the behavior of walking on a rotating rod. In contrast, some other drugs (e.g., benzodiazepine anxiolytics) only affect marble burying and nestlet shredding at motor-impairing doses. The present methods might therefore provide one piece of in vivo information for the discovery of novel chemical treatment solutions for the symptoms of OCD.
强迫症（OCD）的患病率很高，用于治疗强迫症的药物疗效有限且存在副作用问题。体内预测模型的缺乏在一定程度上阻碍了治疗强迫症的改良药物的发现。本单元简要概述了两种可能具有这种预测效用的方法。埋球和撕碎筑巢材料是小鼠中高频且重复自发出现的两种行为。这些急性体内试验相对容易进行。通过在旋转杆上行走的行为评估，选择性5-羟色胺再摄取抑制剂可减少这些行为，且不会产生运动副作用。相比之下，其他一些药物（如苯二氮䓬类抗焦虑药）仅在产生运动损伤的剂量下才会影响埋球和撕碎筑巢材料的行为。因此，目前的方法可能为发现治疗强迫症症状的新型化学治疗方案提供一条体内信息。
