Yang C R, Bai Y Y, Ruan C S, Zhou H F, Liu D, Wang X F, Shen L J, Zheng H Y, Zhou X F
Department of Pathology, Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China.
Neurotox Res. 2015 Feb;27(2):129-42. doi: 10.1007/s12640-014-9498-4. Epub 2014 Nov 4.
Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident-intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression.
抑郁症是最常见的慢性精神障碍之一，是患者发病和死亡的主要原因。抑郁症常导致攻击和防御行为，但其潜在机制尚不清楚。我们提出，抑郁症中的攻击行为可以在动物实验中进行模拟。在本研究中，我们使用慢性不可预测轻度应激（CUMS）范式成功建立了小鼠抑郁症模型，并分别通过居住者/入侵者测试和社会优势管测试（SDTT）检测了啮齿动物的攻击和社会优势行为。暴露于CUMS的小鼠在居住者-入侵者测试中表现出防御、攻击和侵略行为增加。在SDTT中，这些小鼠表现出增强的社会优势。这些改变与海马中MAP-2表达的降低有关，而β-微管蛋白表达未检测到差异。此外，抗抑郁药氟西汀的治疗逆转了攻击行为，而没有降低CUMS诱导的社会优势行为。然而，氟西汀确实有效地逆转了海马中MAP-2表达的变化。此外，非特异性三环抗精神病药物氯氮平逆转了暴露于CUMS小鼠的所有症状，包括攻击倾向、冲动暴力、社会优势行为和海马中的MAP-2表达。结果表明，诸如竞争和社会优势等社会适应不良可能与多巴胺能系统而非血清素能系统以及海马树突结构蛋白MAP-2有关。因此，优势可以与攻击分开。本研究表明，暴露于CUMS的小鼠中攻击/敌意和社会等级/优势增加，从而为进一步研究抑郁症相关攻击的诊断和治疗提供了一个极好的模型。
