近日来自西安交通大学的研究人员在国际著名学术刊物《公共科学图书馆—综合》（PLoS ONE）上发表了题目为“Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress”的研究论文。

该论文的第一作者是西安交通大学附属一院精神心理科马现仓副教授，通讯作者是高成阁教授和西安交通大学医学院的党永辉博士。

既往研究证实应激性生活事件是重症抑郁（major depressive disorder）的重要易感因素之一，给予啮齿类动物以长期的难以预料的各种不威胁生存的应激，可以引起类似人类的抑郁和焦虑样行为，这也是国际上通行的建立抑郁动物模型的方法之一，即为“慢性不可预期温和应激（chronic unpredictable mild stress, CUMS）”抑郁模型。但是这一模型在小鼠的再现性比较低，比较难以建立。有文献报道单独饲养的成年雄性小鼠对同性的攻击性增强。

该研究小组在国家自然科学基金的资助下，利用小鼠的这一生物特性，在常用各种应激源中引入孤养以及随机相互攻击的应激，成功建立小鼠CUMS模型，并发现这一方法优于使用其它常见温和应激。这一结果，对于成功建立抑郁小鼠模型具有重要启示，对于一些临床现象也有启迪作用。

该研究小组目前正在利用这一新的模型进行抑郁症神经生物学机制和干预性治疗的深入研究。该文章的发表标志着一附院精神心理科在抑郁症的基础研究方面迈上一个新的台阶。

原文出处：

PLoS ONE    doi:10.1371/journal.pone.0020955

Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

Xian-cang Ma, Dong Jiang, Wen-hui Jiang, Fen Wang, Min Jia1, Jin Wu, Kenji Hashimoto, Yong-hui Dang, Cheng-ge Gao

Background

Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression.

Methodology/Principal Findings

C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.

Conclusions/Significance

These findings show that social isolation-induced aggression could potentiate anxiety and depressive -like behaviors in isolated male mice subjected to CMS.

Funding: The project was supported by the National Natural Science Foundation of China (No. 30700261 and No. 30870887) and the Ministry of Science and Technology of China (No. 2009DFA31080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: Kenji Hashimoto is a member of Editorial Board of PLoS ONE. The other authors have declared that no competing interests exist.