Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice
Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice
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DOI：
10.1073/pnas.0505312102
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发表时间：
2005-11-01
影响因子：
11.1
通讯作者：
Nishimori, K
中科院分区：
文献类型：
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作者：
Takayanagi, Y;Yoshida, M;Nishimori, K
催产素受体（OXTR）及其配体催产素（OXT）调节生殖生理（即分娩和哺乳）和社会性行为。为了确定OXTR的基本功能，我们产生了OXTR基因零突变的小鼠（OXTR(-/-)），并将它们与Oxt缺陷小鼠（Oxt(-/-)）进行比较。Oxtr（-/-）小鼠存活，在生育能力和生殖行为方面没有明显缺陷。Oxtr（-/-）母鼠表现出正常的分娩，但在哺乳和母性喂养方面表现出缺陷。幼雄牛（-/-）发出的超声波发声比野生型的同伴更少，以应对社会隔离。成年oxr（-/-）男性也表现出社会歧视的缺陷和攻击行为的增加。来自Oxt（-/-）坝的配体雄性Oxt（-/-）表现出相似的高攻击性，而来自Oxt（+/-）坝的雄性则没有。这些数据表明，OXT/OXTR系统在塑造成人攻击行为方面具有发展作用。我们的研究表明，OXTR在调节社会行为的几个方面起着关键作用，并可能对以社会行为缺陷为特征的发展性精神障碍具有重要意义。
The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr(-/-)) and compared them with OXT-deficient (Oxt(-/-)) mice. Oxtr(-/-) mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr(-/-) dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr(-/-) males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr(-/-) males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt(-/-) males from Oxt(-/-) dams, but not from Oxt(+/-) dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.