Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice
Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice
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DOI：
10.1038/sj.npp.1300360
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发表时间：
2004-03-01
影响因子：
7.6
通讯作者：
Young, LJ
中科院分区：
文献类型：
--
作者：
Bielsky, IF;Hu, SB;Young, LJ
大量证据表明精氨酸加压素（AVP）在许多社会和非社会行为的调节中起着重要作用，包括情绪。大脑中存在两种AVP受体，即VIa和VIb亚型，并且缺乏使用选择性激动剂或拮抗剂的明确药理学数据，使得难以确定哪种受体负责AVP介导的行为效应。在这里，我们报告了一个无效突变的VIa受体（VIoR）在雄性小鼠的行为影响。缺乏功能性VIaR（VIaRKO）的雄性小鼠表现出显著减少的焦虑样行为和社会识别的严重损害。在空间和非社会性嗅觉学习和记忆任务中表现正常。AVP的急性中枢给药强烈刺激了野生型（VVT）中的刻板抓挠和自动梳理，但不是VlaRKO雄性。AVP和催产素（OT）mRNA和OT受体结合水平在VVT和VlaRKO小鼠中相似。鉴于目前的研究结果，V I aR可能为社交和情感障碍（包括自闭症和焦虑症）提供新的潜在药理学靶点。
Considerable evidence suggests that arginine vasopressin (AVP) is critically involved in the regulation of many social and nonsocial behaviors, including emotionality. The existence of two AVP receptors in the brain, namely the VIa and VIb subtypes, and the lack of clear pharmacological data using selective agonists or antagonists, make it difficult to determine which receptor is responsible for the AVP-mediated effects on behavior. Here we report the behavioral effects of a null mutation in the VIa receptor (VIoR) in male mice. Male mice lacking functional VIaR (V I aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V IaRKC) performed normally on spatial and nonsocial olfactory learning and memory tasks. Acute central administration of AVP robustly stimulated stereotypical scratching and autogrooming in wild-type (VVT), but not V I aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding levels were similar in VVT and V I aRKO mice. Given the current findings, the V I aR may provide a novel potential pharmacological target for social and affective disorders including autism, and anxiety disorders.