Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry
Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry
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DOI：
10.1016/j.bbr.2008.01.003
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发表时间：
2008-06-03
影响因子：
2.7
通讯作者：
Koolhaas, Jaap M.
中科院分区：
文献类型：
--
作者：
Caramaschi, Doretta;de Boer, Sietse F.;Koolhaas, Jaap M.
最近关于啮齿动物攻击模型对人类暴力的有效性的评论已经解决了雄性啮齿动物攻击行为中病理，适应不良，暴力形式的攻击维度。在正常和病理形式的攻击行为调节的神经生物学机制中，血清素起着重要作用。然而，详细机制的结果仍然是混乱和有争议的，主要是因为很难从啮齿动物到人类的精神病理行为进行外推。我们的目的是研究血清素在病理性攻击中的作用。我们将基因选择为高（SAL， TA， NC900系）和低（LAL， TNA, NC100）攻击水平的小鼠（RRI小鼠）置于重复的居民入侵者体验中（RRI小鼠）或作为对照程序处理（CTR小鼠）。我们记录的病理攻击参数是对雌性的攻击和与对手之间缺乏交流。在同样的小鼠中，我们测量了前额叶皮层的单胺水平，前额叶皮层是一个强烈参与调节动机行为的大脑区域。我们的研究结果表明，SAL小鼠的攻击倾向增强，表现出最病态的表型，不顾对手的性别，高度的领土行为模式，对从属信号的低敏感性。相比之下，TA和NC900增强了它们的攻击倾向和对对手信号的低辨别能力，而不会对雌性表现出冒犯。与CTR小鼠相比，在重复的居住者-入侵者体验后，SAL小鼠前额叶皮层的血清素水平显著低于LAL小鼠，而多巴胺周转率显著较高。血清素周转率在所有RRI小鼠中都显著降低，没有品系差异。与低攻击性小鼠相比，攻击性小鼠TA和NC900系的去甲肾上腺素水平显著降低，而重复的“居民-入侵者”体验没有影响。我们的结论是，社会经验改变了前额叶皮层的神经化学，引发了病理上的攻击性表型。(C) 2008 Elsevier B.V.版权所有
Recent reviews on the validity of rodent aggression models for human violence have addressed the dimension of pathological, maladaptive, violent forms of aggression in male rodent aggressive behaviour. Among the neurobiological mechanisms proposed for the regulation of aggressive behaviour in its normal and pathological forms, serotonin plays a major role. However, the results on the detailed mechanism are still confusing and controversial, mainly because of difficulties in extrapolating from rodent to human psychopathological behaviour. Our aim was to investigate the involvement of serotonin in pathological aggression. We subjected mice genetically selected for high (SAL, TA, NC900 lines) and low (LAL, TNA, NC100) aggression levels to a repeated resident-intruder experience (RRI mice) or to handling as a control procedure (CTR mice). Pathological aggression parameters we recorded were aggression towards females and lack of communication between the resident and its opponent. In the same mice, we measured the monoamine levels in the prefrontal cortex, a brain region strongly involved in the regulation of motivated behaviour. Our results show that SAL mice augmented their proneness to attack and showed the most pathological phenotype, with disregard of the opponent's sex, high territorial behavioural patterns, and low sensitivity to signals of subordination. In contrast, TA and NC900 augmented their proneness to attack and low discrimination of the opponent's signals, without showing offence towards females. After repeated resident-intruder experience, serotonin levels in the prefrontal cortex were significantly lower in SAL than in LAL whereas dopamine turnover was significantly higher, compared to CTR mice. Serotonin turnover was significantly reduced in all RRI mice, with no strain differences. Noradrenaline was significantly lower in aggressive mice of the TA and NC900 lines compared to their low-aggressive counterparts, with no effect of the repeated resident-intruder experience. We conclude that social experience changes prefrontal cortex neurochemistry and elicits pathologically aggressive phenotypes. (C) 2008 Elsevier B.V. All rights reserved.