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用不同实验小鼠品系建立精神分裂症的动物模型

吴金华, 邹洪, 于军, 周雪东, 谢青莲, 金玫蕾

中科院上海生命科学研究院生物工程研究中心.上海 200233

摘要

基于精神分裂症的谷氨酸功能紊乱假说,实验用N-甲基-D-天门冬氨酸(NMDA)非竞争性受体拮抗剂MK801(5-甲基二氢二苯并环庚稀亚氨马来酸或地卓西平马来酸盐)作用于实验小鼠,观察到类似精神分裂症的症状;移动加快(hyperlocomotion)和刻板性动作(stereotypy),建立了可用仪器测定的两项量化指标。根据作用于近交系BALB/c小鼠的MK801的剂量优化结果,用0.6mg/kg体重的MK801剂量初步建立了精神分裂症小鼠模型,并用近交系C57BL/6小鼠成功重复了上述实验。进一步用系列剂量的MK801作用于远交群ICR小鼠,同样也诱发了类似精神分裂症的症状。用目前临床上常用的抗精神分裂症药物利培酮作用于已建立的BALB/c小鼠和C57BL/6小鼠的精神分裂症模型,结果表明利培酮能显著地抑制两品系模型小鼠的类似精神分裂症的症状。实验结果证明:用MK801作用于实验小鼠建立精神分裂症动物模型是可行的。

关键词： 精神分裂症; 动物模型; MK801; 移动加快; 刻板性动作; 利培酮

Animal models of schizophrenia using different laboratory mouse strains

Wu Jinhua, Zou Hong, Yu Jun, Zhou Xuedong, Xie Qinglian, Jin Meilei

Shanghai Research Center of Biotechnology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences.Shanghai 200233

Abstract

These results show that MK801 induces schizophrenia-like symptoms in both inbred and outbred mice. Risperidone, an atypical antipsychotic drug for treating schizophrenia in human, was used in the schizophrenia models using BALB/c and C57BL/6 mice. The results indicated that risperidone dose-dependently inhibited the MK801-induced schizophrenia-like symptoms in BALB/c and C57BL/6 mice. Thus, our results indicate that the MK801-induced behaviors may serve as useful mouse models of schizophrenia.

Key words: Schizophrenia;Animal model;MK801;Hyperlocomotion;Stereotypy;Risperidone

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引用本文：

吴金华, 邹洪, 于军, 周雪东, 谢青莲, 金玫蕾. 用不同实验小鼠品系建立精神分裂症的动物模型[J]. 生理学报 2003; 55 (4): .

Wu Jinhua, Zou Hong, Yu Jun, Zhou Xuedong, Xie Qinglian, Jin Meilei. Animal models of schizophrenia using different laboratory mouse strains. Acta Physiol Sin 2003; 55 (4): (in Chinese with English abstract).