Veenema Alexa H, Bredewold Remco, Neumann Inga D
Department of Behavioral Neuroendocrinology, Institute of Zoology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
Psychoneuroendocrinology. 2007 Jun;32(5):437-50. doi: 10.1016/j.psyneuen.2007.02.008. Epub 2007 Apr 11.
Early life stress, in particular child abuse and neglect, is an acknowledged risk factor for the development of pathological anxiety and aggression. In rodents, 3-h daily maternal separation (MS) during the first 2 weeks of life is an established animal model of early life stress and has repeatedly been shown to increase anxiety and stress responsiveness in adulthood. However, preclinical studies on the effects of postnatal stress on adult aggression are limited. The present study investigated whether MS affects intermale aggression and/or maternal aggression in C57BL/6 mice. In both adult male and virgin female mice, MS elevated anxiety-related behavior as tested on the elevated plus-maze, in the open field and during novel object exploration. The latency to attack an unknown male intruder, as assessed with the resident-intruder test, was significantly longer in MS male mice compared with control male mice. In contrast, the latency to attack a novel male intruder was significantly shorter in MS females compared with control females on days 3 and 5 of lactation. These opposite effects of MS can be explained by the fact that intermale and maternal aggression are two different forms of aggression, and hence, might be modulated by different neurobiological pathways. Indeed, in the paraventricular nucleus of the hypothalamus, MS was found to selectively increase vasopressin immunoreactivity in males, whereas MS selectively decreased oxytocin immunoreactivity in lactating females. In conclusion, MS has long-lasting and differential effects on adult intermale and maternal aggression in C57BL/6 mice. Alterations in hypothalamic vasopressin and oxytocin immunoreactivity may, in part, underlie the opposite effects of MS on intermale and maternal aggression. The MS paradigm represents a promising animal model to reveal underlying mechanisms of aggressive behavioral dysfunctions associated with early life stress.
早年生活应激，尤其是儿童期虐待和忽视，是公认的病理性焦虑和攻击行为发展的危险因素。在啮齿动物中，出生后第1周的每天3小时母婴分离（MS）是一种既定的早年生活应激动物模型，并且反复表明其会增加成年期的焦虑和应激反应性。然而，关于产后应激对成年期攻击行为影响的临床前研究有限。本研究调查了母婴分离是否会影响C57BL/6小鼠的雄性间攻击行为和/或母性攻击行为。在成年雄性和未孕雌性小鼠中，母婴分离均增加了高架十字迷宫、旷场和新物体探索测试中与焦虑相关的行为。通过定居者-入侵者测试评估，母婴分离的雄性小鼠攻击未知雄性入侵者的潜伏期明显长于对照雄性小鼠。相比之下，在哺乳期第3天和第5天，母婴分离的雌性小鼠攻击新雄性入侵者的潜伏期明显短于对照雌性小鼠。母婴分离的这些相反作用可以通过以下事实来解释，即雄性间攻击行为和母性攻击行为是两种不同形式的攻击行为，因此可能由不同的神经生物学途径调节。事实上，在下丘脑室旁核中，发现母婴分离会选择性增加雄性小鼠的加压素免疫反应性，而母婴分离会选择性降低哺乳期雌性小鼠的催产素免疫反应性。总之，母婴分离对C57BL/6小鼠成年期的雄性间攻击行为和母性攻击行为具有长期且不同的影响。下丘脑加压素和催产素免疫反应性的改变可能部分是母婴分离对雄性间攻击行为和母性攻击行为产生相反作用的基础。母婴分离范式是一种有前景的动物模型，可用于揭示与早年生活应激相关的攻击行为功能障碍的潜在机制。
