Crawley Jacqueline N, Chen Thomas, Puri Amit, Washburn Richard, Sullivan Timothy L, Hill Joanna M, Young Nancy B, Nadler Jessica J, Moy Sheryl S, Young Larry J, Caldwell Heather K, Young W Scott
Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
Neuropeptides. 2007 Jun;41(3):145-63. doi: 10.1016/j.npep.2007.02.002. Epub 2007 Apr 8.
Oxytocin mediates social affiliation behaviors and social memory in rodents. It has been suggested that disruptions in oxytocin contribute to the deficits in reciprocal social interactions that characterize autism. The present experiments employed a new social approach task for mice which is designed to detect low levels of sociability, representing the first diagnostic criterion for autism. Two lines of oxytocin knockout mice were tested, the National Institute of Mental Health line in Bethesda, and the Baylor/Emory line at the University of North Carolina in Chapel Hill. Similar methods were used for each line to evaluate tendencies to spend time with a stranger mouse versus with an inanimate novel object with no social valence. Adult C57BL/6J males were tested identically, as controls to confirm the robustness of the methods used in the social task. Comprehensive phenotyping of general health, neurological reflexes, olfactory and other sensory abilities, and motor functions was employed to assess both lines. No genotype differences were detected in any of the control measures for either line. Normal sociability, measured as time spent with a novel stranger mouse as compared to time spent with a novel object, was seen in both the NIMH and the Baylor/Emory lines of oxytocin null mutants, heterozygotes, and wild-type littermate controls. Normal preference for social novelty, measured as time spent with a second novel stranger as compared to time spent with a more familiar mouse, was seen in both the NIMH and the Baylor/Emory lines of oxytocin null mutants, heterozygotes, and wild-type littermate controls, with minor exceptions. Similar behavioral results from two independent targeted gene mutations, generated with different targeting vectors, bred on different genetic backgrounds, and tested in different laboratory environments, corroborates the negative findings on sociability in oxytocin mutant mice. Intact tendencies to spend time with another mouse versus with a novel object, in both lines of oxytocin knockouts, supports an interpretation that oxytocin plays a highly specific role in social memory, but is not essential for general spontaneous social approach in mice.
催产素介导啮齿动物的社会依恋行为和社会记忆。有人提出，催产素的紊乱会导致自闭症所特有的相互社会互动缺陷。本实验采用了一种针对小鼠的新的社会接近任务，该任务旨在检测低水平的社交能力，这是自闭症的首要诊断标准。对两种催产素基因敲除小鼠品系进行了测试，一种是位于贝塞斯达的美国国立精神卫生研究所品系，另一种是位于教堂山的北卡罗来纳大学的贝勒/埃默里品系。对每个品系都采用了类似的方法来评估与陌生小鼠相处和与无社会价值的无生命新物体相处的时间倾向。成年C57BL/6J雄性小鼠也进行了相同的测试，作为对照以确认社会任务中所用方法的稳健性。采用全面的表型分析来评估两个品系的一般健康状况、神经反射、嗅觉和其他感觉能力以及运动功能。在两个品系的任何对照指标中均未检测到基因型差异。在催产素基因敲除突变体、杂合子和野生型同窝对照的美国国立精神卫生研究所品系和贝勒/埃默里品系中，均观察到正常的社交能力，即与新陌生小鼠相处的时间与与新物体相处的时间相比。在催产素基因敲除突变体、杂合子和野生型同窝对照的美国国立精神卫生研究所品系和贝勒/埃默里品系中，除了少数例外，均观察到对社会新奇性的正常偏好，即与第二个新陌生小鼠相处的时间与与更熟悉的小鼠相处的时间相比。来自两个独立的靶向基因突变的相似行为结果，这些突变是用不同的靶向载体产生的，在不同的遗传背景上繁殖，并在不同的实验室环境中进行测试，证实了催产素突变小鼠社交能力的阴性结果。在两个催产素基因敲除品系中，与另一只小鼠相处和与新物体相处的时间倾向完整，这支持了一种解释，即催产素在社会记忆中起高度特定的作用，但对小鼠的一般自发社会接近并非必不可少。
