上海交通大学学报(医学版) ›› 2015, Vol. 35 ›› Issue (10): 1436-.doi: 10.3969/j.issn.1674-8115.2015.10.002

• 论著(基础研究) • 上一篇    下一篇

Enhancement of effect of risperidone on cognitive function of schizophrenic mice by fluoxetine

QIAO Ying1, ZHANG Lei2, HE Shen1, SHENG Jian-hua1, WANG Hui-fang1, LI Hua-fang1   

  1. 1.Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai200030, China; 2.Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai200025, China
  • 出版日期:2015-10-20 发布日期:2015-12-22
  • 通讯作者: WANG Hui-fang (王慧芳), 电子信箱: huifang1808@sina.com; LI Hua-fang(李华芳), 电子信箱: Drli_shanghai@163.com
  • 基金资助:

    Special Project from Ministry of Science and Technology of China (2012ZX09303-003); Shanghai Natural Science Foundation (13ZR1435800); Training Project of Excellent Talents in Shanghai (XBR2011049).

Enhancement of effect of risperidone on cognitive function 

QIAO Ying1, ZHANG Lei2, HE Shen1, SHENG Jian-hua1, WANG Hui-fang1, LI Hua-fang1   

  1. 1.Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai200030, China; 2.Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai200025, China
  • Online:2015-10-20 Published:2015-12-22
  • Supported by:

    Special Project from Ministry of Science and Technology of China (2012ZX09303-003); Shanghai Natural Science Foundation (13ZR1435800); Training Project of Excellent Talents in Shanghai (XBR2011049)

Abstract:

Objective To explore the molecular mechanism of enhancing the effect of risperidone on the cognitive function of schizophrenic mice by fluoxetine.MethodsSchizophrenic mice were injected with MK-801 and drugs (fluoxetine and/or risperidone) were administrated orally 30 min before the injection of MK-801. Mice of the control group administrated the same dose of normal saline. The cognitive function, distance of activity, and stereotyped behavior of mice were observed. The expressions of key parameters of MEK/ERK pathway in hippocampus were detected by Western blotting or real-time qPCR. The participation of MEK/ERK pathway in isolated hippocampal neuron injuries induced by MK-801 mediation was also analyzed.ResultsThe mice of MK-801 group showed prolonged activity distance, increased stereotyped behavior scores, and cognitive impairment. Expressions of pMEK/MEK, pERK/ERK1/2, MMP2/9, and TIMP1/2 of the MK-801 group increased. The aforementioned proteins of drug administration groups decreased dramatically. For schizophrenic mice, fluoxetine enhanced effects of risperidone in normalizing abnormal behaviors, affecting cognitive function, and unusual protein expressions (P<0.05). Results of in vitro experiments were similar to those of in vivo experiments. ConclusionFluoxetine enhances the anti-schizophrenic effect of risperidone by normalizing the activated MEK/ERK signaling pathway.

Key words:

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