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早期社会隔离构建精神分裂症动物模型的行为学和神经生物学特征

雷铭, 罗路, 马士棋, 张研, 吴玺宏, 李量^*

北京大学心理学系，北京大学生命科学学院，机器感知与智能教育部重点实验室，北京 100871

摘要

发育早期的不良事件会对动物和人类的大脑发育及成年后的行为产生重要影响。早期社会隔离能引起人和动物的行为模式及神经系统结构产生持久性改变，本文从认知行为水平及细胞分子水平总结了社会隔离对实验动物造成的影响。动物隔离实验表明，隔离对认知行为方面造成的影响主要包括：运动增多，惊反射和前脉冲抑制异常及学习、记忆功能下降。神经递质方面的影响主要包括：伏隔核、杏仁核及中脑边缘系统内多巴胺的活性提高，内侧前额叶多巴胺的活性降低，同时海马、伏隔核等脑区内5-羟基色胺酸受体活性异常，多个脑区谷氨酸代谢异常。最后，早期社会隔离还会引起海马、内侧前额叶、杏仁核、伏隔核等脑区细胞凋亡的异常。多脑区多种神经递质的异常和细胞凋亡的异常可能是导致动物行为出现异常的神经机制。鉴于早期社会隔离动物表现出的行为、神经递质、细胞凋亡方面的异常与精神分裂症等发展性精神疾病的症状密切相关，因此早期社会隔离可以作为一种有效的研究精神分裂症的动物模型。

关键词： 早期社会隔离; 精神分裂症; 前脉冲抑制; 神经递质; 细胞凋亡

[Behavioral and neurobiological abnormalities induced by social isolation as a useful animal model of schizophrenia.] [Article in Chinese]

LEI Ming, LUO Lu, MA Shi-Qi, ZHANG Yan, WU Xi-Hong, LI Liang^*

Department of Psychology, College of Life Sciences, Speech and Hearing Research Center, Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing 100871, China

Abstract

Social isolation influences the development of the brain, causing dysfunctions at behavioral, cellular and molecular levels. The present paper summarizes the abnormalities induced by social isolation in behaviors, neurotransmitters and cell apoptosis. At the behavioral level, social isolation induces hyperlocomotion, abnormalities in startle reflex and prepulse inhibition (PPI), and dysfunctions in conditioned learning, reversal learning and memory. Moreover, social isolation causes changes of neurotransmitters, such as the increase of dopamine in the nucleus accumbens, the amygdala and other brain regions in the limbic system, the decrease of dopamine in medial prefrontal cortex, the decrease of 5-HT in the nucleus accumbens and the hippocampus, and changes of glutamine in the prefrontal cortex. Finally, social isolation affects cell apoptosis in different brain areas, such as the medial prefrontal cortex, amygdala, nucleus accumbens, and hippocampus. Both the changes in neurotransmitters and cell apoptosis may contribute to the behavioral dysfunctions in social isolated rats. Since schizophrenic patients have similar abnormalities in behaviors and neurotransmitters, isolation rearing can be used as a useful animal model of schizophrenia.

Key words: social isolation; schizophrenia; prepulse inhibition; neurotransmitter; cell apoptosis

收稿日期：2012-04-30　　录用日期：2012-11-23

通讯作者：李量　　E-mail: liangli@pku.edu.cn

引用本文：

雷铭, 罗路, 马士棋, 张研, 吴玺宏, 李量. 早期社会隔离构建精神分裂症动物模型的行为学和神经生物学特征[J]. 生理学报 2013; 65 (1): 101-108.

LEI Ming, LUO Lu, MA Shi-Qi, ZHANG Yan, WU Xi-Hong, LI Liang. [Behavioral and neurobiological abnormalities induced by social isolation as a useful animal model of schizophrenia.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (1): 101-108 (in Chinese with English abstract).