颜 慧, 李树玲, 苏瑞斌, 宫泽辉. 药物诱发性精神分裂症小鼠模型的建立与应用J. 药学学报, 2013,48(4): 484-488.
引用本文: 颜 慧, 李树玲, 苏瑞斌, 宫泽辉. 药物诱发性精神分裂症小鼠模型的建立与应用J. 药学学报, 2013,48(4): 484-488.
YAN Hui, LI Shu-ling, SU Rui-bin, GONG Ze-hui. Establishment and application of a mouse model for drug-induced schizophreniaJ. 药学学报, 2013,48(4): 484-488.
Citation: YAN Hui, LI Shu-ling, SU Rui-bin, GONG Ze-hui. Establishment and application of a mouse model for drug-induced schizophreniaJ. 药学学报, 2013,48(4): 484-488.

药物诱发性精神分裂症小鼠模型的建立与应用

Establishment and application of a mouse model for drug-induced schizophrenia

  • 摘要:

    根据精神分裂症患者认知混乱和情绪异常等症状, 采用自发活动和前脉冲抑制 (PPI) 为评价指标, 利用NMDA受体拮抗——地卓西平马来酸盐 (+) MK-801 为诱导剂, 建立了药物致小鼠精神分裂症模型, 并考察了阳性药氯氮平的干预作用。结果显示, 给予MK-801可使小鼠自发活动显著增强, 前脉冲抑制功能显著受损, 预先给予氯氮平可显著改善两个指标的异常, 使其恢复至与正常对照组无显著性差异。结果表明, 所建立的评价模型可用于抗精神分裂症药物的快速筛选。

     

    Abstract:

    Schizophrenia, described as the worst disease affecting mankind, is a severe and disabling mental disorder.  Schizophrenia is characterized by complicated symptoms and still lacks a diagnostic neuropathology, so developing schizophrenia animal models which have quantifiable measures tested in a similar fashion in both humans and animals will play a key role in new therapeutic approaches.  According to the symptoms of cognitive impairment and emotional disorder, the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 was applied to induce schizophrenia-like behavior in mice.  Locomotor activity and prepulse inhibition (PPI) were selected as indices and the effect of clozapine was also investigated in this model.  The results showed that compared with the normal group, MK-801-treated mice exhibited significantly increased locomotor activity and impaired PPI, and pre-exposure to clozapine could ameliorate the abnormality and make it back to normal level.  These findings suggest that the model we established could be a useful tool for antipsychotic drug screening.

     

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