Caramaschi Doretta, de Boer Sietse F, de Vries Han, Koolhaas Jaap M
Department of Behavioural Physiology, Biology Centre, University of Groningen, Haren, The Netherlands.
Behav Brain Res. 2008 Jun 3;189(2):263-72. doi: 10.1016/j.bbr.2008.01.003. Epub 2008 Jan 15.
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.
近期有关啮齿动物攻击模型对人类暴力行为有效性的综述，探讨了雄性啮齿动物攻击行为中病理性、适应不良性、暴力性攻击形式的维度。在提出的用于调节正常和病理性攻击行为的神经生物学机制中，血清素起着主要作用。然而，关于详细机制的结果仍然令人困惑且存在争议，主要是因为从啮齿动物推断到人类心理病理行为存在困难。我们的目的是研究血清素在病理性攻击中的作用。我们将经过基因筛选具有高（SAL、TA、NC900品系）和低（LAL、TNA、NC100）攻击水平的小鼠，分别进行重复的住家-入侵者实验（RRI小鼠）或作为对照程序进行处理（CTR小鼠）。我们记录的病理性攻击参数包括对雌性的攻击以及住家小鼠与其对手之间缺乏交流。在同一批小鼠中，我们测量了前额叶皮质中的单胺水平，前额叶皮质是一个在调节动机行为中起重要作用的脑区。我们的结果表明，SAL小鼠增加了其攻击倾向，并表现出最病理性的表型，即无视对手性别、具有高度领地行为模式以及对从属信号的低敏感性。相比之下，TA和NC900小鼠增加了其攻击倾向且对对手信号的辨别能力较低，但未表现出对雌性的攻击行为。经过重复的住家-入侵者实验后，与LAL小鼠相比，SAL小鼠前额叶皮质中的血清素水平显著降低，而与CTR小鼠相比，多巴胺周转率显著升高。所有RRI小鼠的血清素周转率均显著降低，且无品系差异。与低攻击性的对应品系相比，TA和NC900品系的攻击性小鼠中的去甲肾上腺素显著降低，重复的住家-入侵者实验对此没有影响。我们得出结论，社会经历会改变前额叶皮质的神经化学，并引发病理性攻击表型。
