Kubota Hisayoshi, Zhang Xinjian, Khalili Masoumeh, Zhou Xinzhu, Wen Yu, Nagai Taku
Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, Toyoake 470-1192, Aichi, Japan.
Fujita Mind-Brain Research & Innovation Center for Drug Generation (Fujita Mind-BRIDGe), Fujita Health University, Toyoake 470-1192, Aichi, Japan.
Int J Mol Sci. 2025 May 28;26(11):5184. doi: 10.3390/ijms26115184.
Schizophrenia is a psychiatric disorder characterized by positive, negative, and cognitive symptoms. MK-801, an N-methyl-D-aspartate receptor antagonist, has been used to induce schizophrenia-like behaviors in animal models. Here, we employed IntelliCage, an automated system used for tracking behavior, to assess schizophrenia-like behaviors in MK-801-treated mice under semi-naturalistic conditions. Mice that had been treated with MK-801 for 2 weeks were analyzed for locomotion, emotional, and cognitive functions. Repeated MK-801-treated mice exhibited transient hyperactivity in a novel environment, without significant changes in overall circadian activity. Sucrose preference remained intact, suggesting preserved reward sensitivity. However, less time spent in the corner during the early phase of the competition test indicated reduced competitive behavior for limited water rewards. In the behavioral flexibility test, repeated MK-801-treated mice showed impaired reversal learning, suggesting reduced cognitive flexibility, although the acquisition of initial place discrimination was comparable to that observed in control mice. These behavioral impairments parallel core symptoms of schizophrenia, particularly in the social and cognitive domains. Our findings demonstrate the utility of IntelliCage in detecting behavioral phenotypes over prolonged periods in group-housed settings. This study provides an ecologically valid platform for assessing schizophrenia-like behaviors and may facilitate the development of translationally relevant therapeutic interventions.
精神分裂症是一种以阳性、阴性和认知症状为特征的精神障碍。MK-801是一种N-甲基-D-天冬氨酸受体拮抗剂，已被用于在动物模型中诱导类似精神分裂症的行为。在此，我们使用IntelliCage（一种用于跟踪行为的自动化系统）在半自然条件下评估MK-801处理的小鼠的类似精神分裂症的行为。对用MK-801处理2周的小鼠进行运动、情绪和认知功能分析。反复用MK-801处理的小鼠在新环境中表现出短暂的多动，其整体昼夜活动没有显著变化。蔗糖偏好保持不变，表明奖励敏感性得以保留。然而，在竞争测试早期阶段在角落花费的时间减少表明对有限水奖励的竞争行为减少。在行为灵活性测试中，反复用MK-801处理的小鼠表现出逆向学习受损，表明认知灵活性降低，尽管初始位置辨别学习与对照小鼠中观察到的相当。这些行为障碍与精神分裂症的核心症状相似，尤其是在社交和认知领域。我们的研究结果证明了IntelliCage在群体饲养环境中长时间检测行为表型的效用。本研究为评估类似精神分裂症的行为提供了一个生态有效的平台，并可能促进与转化相关的治疗干预措施的开发。
