Impaired nitric oxide synthase signaling dissociates social investigation and aggression
Impaired nitric oxide synthase signaling dissociates social investigation and aggression
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DOI：
10.1037/0735-7044.121.2.362
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发表时间：
2007-04-01
影响因子：
1.9
通讯作者：
Nelson, Randy J.
中科院分区：
文献类型：
--
作者：
Trainor, Brian C.;Workman, Joanna L.;Nelson, Randy J.
社交退缩和攻击性增强的结合是几种精神障碍的特征。大多数先前的研究都是独立研究社会行为和攻击的神经化学基础，而不是这些行为是如何协调调节的。神经性一氧化氮合酶（nNOS）产生气态一氧化氮，一氧化氮作为一种神经递质，已知影响几种类型的行为，包括交配和攻击。与野生型小鼠相比，我们观察到nNOS敲除小鼠对铁丝屏障后的入侵者表现出较低的行为反应。在选择性nNOS抑制剂3-溴-7-硝基茚唑（3BrN）处理的小鼠中也观察到类似的结果。在适应-非适应试验中，与油处理的动物相比，3BrN处理没有阻断对雄性尿液的识别，但缩短了调查时间。最后，nNOS敲除小鼠和3BrN处理小鼠的攻击性分别显著高于野生型和油处理小鼠。总的来说，这些行为影响在成对居住的雄性中比在单独居住的雄性中不那么明显。因此，nNOS抑制导致表现出社会调查减少和攻击性增加的表型。这些数据表明，在以社交退缩和攻击性增加为特征的精神障碍中，有必要进一步研究nNOS信号。
A combination of social withdrawal and increased aggression is characteristic of several mental disorders. Most previous studies have investigated the neurochemical bases of social behavior and aggression independently, as opposed to how these behaviors are regulated in concert. Neuronal nitric oxide synthase (nNOS) produces gaseous nitric oxide, which functions as a neurotransmitter and is known to affect several types of behavior including mating and aggression. Compared with wild-type mice, we observed that nNOS knockout mice showed reduced behavioral responses to an intruder behind a wire barrier. Similar results were observed in mice treated with the selective nNOS inhibitor 3-bromo-7-nitroindazole (3BrN). In habituation-dishabituation tests, treatment with 3BrN did not block recognition of male urine but did attenuate investigation time compared with oil-treated animals. Finally, nNOS knockout mice and 3BrN treated mice were significantly more aggressive than wild-type and oil-treated males, respectively. In general, these behavioral effects are less pronounced in pair-housed males compared with singly-housed males. Thus, nNOS inhibition results in a phenotype that displays reduced social investigation and increased aggression. These data suggest that further study of nNOS signaling is warranted in mental disorders characterized by social withdrawal and increased aggression.