Bielsky Isadora F, Hu Shuang-Bao, Szegda Kathleen L, Westphal Heiner, Young Larry J
Center for Behavioral Neuroscience, Department of Psychiatry, Emory University, Atlanta, GA 30329, USA.
Neuropsychopharmacology. 2004 Mar;29(3):483-93. doi: 10.1038/sj.npp.1300360.
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 V1a and V1b 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 V1a receptor (V1aR) in male mice. Male mice lacking functional V1aR (V1aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO 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 (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding levels were similar in WT and V1aRKO mice. Given the current findings, the V1aR may provide a novel potential pharmacological target for social and affective disorders including autism, and anxiety disorders.
大量证据表明，精氨酸加压素（AVP）在包括情绪在内的许多社会和非社会行为的调节中起着关键作用。大脑中存在两种AVP受体，即V1a和V1b亚型，且缺乏使用选择性激动剂或拮抗剂的明确药理学数据，这使得难以确定哪种受体负责AVP对行为的介导作用。在此，我们报告雄性小鼠V1a受体（V1aR）基因敲除突变的行为效应。缺乏功能性V1aR的雄性小鼠（V1aRKO）表现出焦虑样行为明显减少以及社会识别能力严重受损。V1aRKO在空间和非社会嗅觉学习及记忆任务中表现正常。急性中枢给予AVP能强烈刺激野生型（WT）雄性小鼠出现刻板抓挠和自我梳理行为，但对V1aRKO雄性小鼠无此作用。WT和V1aRKO小鼠的AVP和催产素（OT）mRNA以及OT受体结合水平相似。基于目前的研究结果，V1aR可能为包括自闭症和焦虑症在内的社会和情感障碍提供一个新的潜在药理学靶点。
