Nitric oxide (NO) is a gaseous neurotransmitter that has important behavioural functions in the vertebrate brain. In this study we compare the impact of decreased nitric NO signalling upon behaviour and neurobiology using both zebrafish and mouse. nitric oxide synthase mutant (nos1-/-) zebrafish show significantly reduced aggression and an increase in anxiety-like behaviour without altered production of the stress hormone cortisol. Nos1-/- mice also exhibit decreased aggression and are hyperactive in an open field test. Upon reduction of NO signalling, monoamine neurotransmitter metabolism is reduced as a consequence of decreased Monoamine oxidase activity. Treatment of nos1-/- zebrafish with the 5-HT receptor 1A agonist 8-OH-DPAT rescues aggression and some aspects of anxiety-like behaviour. Taken together, the interplay between NO and 5-HT appears to be critical to control behaviour. Our cross-species approach challenges the previous notion that reduced neuronal NOS leads to increased aggression. Rather, Nos1 knock-out can also lead to decreased aggression in some situations, a finding that may have implications for future translational research.

中文翻译：

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一氧化氮与单胺氧化酶相互作用以调节攻击性和焦虑样行为

一氧化氮 (NO) 是一种气态神经递质，在脊椎动物大脑中具有重要的行为功能。在这项研究中，我们使用斑马鱼和小鼠比较了减少一氧化氮信号对行为和神经生物学的影响。一氧化氮合酶突变体 (nos1-/-) 斑马鱼表现出显着减少的攻击性和增加的焦虑样行为，而没有改变应激激素皮质醇的产生。Nos1-/- 小鼠也表现出攻击性降低并且在野外测试中过度活跃。当 NO 信号减少时，单胺类神经递质代谢会因单胺氧化酶活性降低而减少。用 5-HT 受体 1A 激动剂 8-OH-DPAT 治疗 nos1-/- 斑马鱼可以挽救攻击性和焦虑样行为的某些方面。综合起来，NO 和 5-HT 之间的相互作用似乎对控制行为至关重要。我们的跨物种方法挑战了先前认为神经元 NOS 减少会导致攻击性增加的观点。相反，在某些情况下，Nos1 敲除也会导致攻击性降低，这一发现可能对未来的转化研究产生影响。