《生命科学》 2023, 35(4): 529-537

MK-801诱导小鼠精神分裂症阳性症状的研究进展

徐进伟 , 李姚浩 , 田碧清 , 刘海鹰 , 王文挺^*

空军军医大学基础医学院神经生物学教研室，西安 710068

摘　要：

精神分裂症是一种有重大社会影响的精神疾病，阳性症状如思维紊乱和行为异常是其典型表现之一，严重影响患者工作生活，甚至给社会带来危害，因此对阳性症状的研究十分重要。目前，大量研究表明N-甲基-D- 天门冬氨酸(N-methyl-D-aspartic acid, NMDA) 受体功能低下可能是导致精神分裂症的重要原因。地卓西平(MK-801) 是一种NMDA 受体非竞争性拮抗剂，可以通过阻滞NMDA 受体导致受体功能减退，并通过与多种神经递质相互作用诱发小鼠表现出精神分裂症样阳性症状。该文对精神分裂症谷氨酸假说进行介绍，然后基于MK-801 诱导小鼠精神分裂症模型，从MK-801 构建模型的特点、给药方式、常见阳性症状表现和可能涉及的作用机制对近些年来的文献进行综述，以期为精神分裂症阳性症状的机制研究及动物模型构建提供了重要的参考依据。

通讯作者：王文挺 , Email:wwt0657@fmmu.edu.cn

Research progress of MK-801 induced positive symptoms of schizophrenia in mice

XU Jin-Wei , LI Yao-Hao , TIAN Bi-Qing , LIU Hai-Ying , WANG Wen-Ting^*

Department of Neurobiology, School of Basic Medicine, Air Force Medical University, Xi’an 710068, China

Abstract:

Schizophrenia is a mental disorder with significant social impact. As one of the major typical symptoms, positive symptoms, such as disordered thinking and abnormal behavior, seriously affect the work and life of patients and even bring harm to society. Recently, many studies have shown that N-methyl-D-aspartic acid (NMDA) receptor hypofunction is a potentially important cause of schizophrenia. Dizocilpine (MK-801) is a non-competitive antagonist of NMDA receptors, which can cause receptor dysfunction by blocking NMDA receptors and induce positive symptoms of schizophrenia in mice by interacting with different neurotransmitters. In this paper, we introduce the glutamate hypothesis of schizophrenia, and then, review the characteristics of the MK-801 induced schizophrenia mouse model, including administration modes, common positive symptoms, and possible mechanisms of action in recent years. These contents serves as a crucial point for comprehending the mechanisms underlying positive symptoms in schizophrenia and developing animal models.

Communication Author：WANG Wen-Ting , Email:wwt0657@fmmu.edu.cn