Tributyltin (TBT), an aromatase inhibitor, has been found to disrupt gametogenesis and reproductive behavior in several fish species. However, whether TBT is capable of affecting other behaviors such as aggressive behavior and fear response in fish and the underlying mode(s) of action remain unclear. To study aggressive behavior, adult zebrafish (Danio rerio) males were continuously exposed to two nominal concentrations of TBT (TBT-low, 100 ng/L and TBT-high, 500 ng/L) for 28 days. To study the fear response, the fish were divided into four groups (Blank and Control, 0 ng/L TBT; TBT-low, 100 ng/L; and TBT-high, 500 ng/L). The fish were then treated with DW (Blank) or with alarm substance (AS) (Control, TBT-low and TBT-high). After exposure, the aggressive behavior of the fish was tested using the mirror test (mirror-biting frequency, approaches to the mirror and duration in approach zone).and fighting test (fish-biting frequency) The mirror-biting frequency, approaches to the mirror, duration in approach zone and fish-biting frequency of the TBT-exposed fish increased significantly compared to those of the control fish, indicating enhanced aggressive behavior. The fear response parameters tested using the novel tank dive test (onset time to the higher half, total duration in the lower half and the frequency of turning) of the TBT-exposed fish were also significantly increased after AS administration, suggesting an enhanced fear response. Further investigation revealed that TBT treatment elevated the plasma level of 11-ketotestosterone (11-KT) and decreased the plasma level of estradiol (E2) in a concentration-dependent manner. Moreover, TBT up-regulated the mRNA levels of ar, c-fos and bdnf1, and suppressed the expression of btg-2 in fish. In addition, exposure to AS increased the plasma level of cortisol and down-regulated the mRNA expression levels of genes involved in 5-HT synthesis (such as tph1b and pet1) in both control and TBT-treated fish. AS significantly suppressed the mRNA level of tph1b, tph2, pet1 and npy in the TBT-high group compared to the control fish. The present study demonstrates that TBT enhances aggressive behavior and fear responses in male zebrafish probably through altering plasma levels of 11-KT, E2 and cortisol and altering the expression of genes involved in the regulation of aggressive behavior (ar, c-fos, bdnf1 and btg-2) and fear responses (tph1b, tph2, pet1 and npy). The present study greatly extends our understanding of the behavioral toxicity of TBT to fish.

中文翻译：

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参与三丁基锡增强雄性斑马鱼攻击行为和恐惧反应的机制。

三丁基锡（TBT）是一种芳香酶抑制剂，已被发现破坏了几种鱼类的配子发生和生殖行为。然而，尚不清楚TBT是否能够影响其他行为，例如侵略性行为和鱼类的恐惧反应以及基本的作用方式。为了研究攻击行为，成年斑马鱼（达尼奥雷里奥）雄性连续暴露于两种标称浓度的TBT（低TBT，100 ng / L和高TBT，500 ng / L），暴露28天。为了研究恐惧反应，将鱼分为四组（空白和对照，TBT为0 ng / L；低至100 ng / L，TBT高；至500 ng / L，TBT高）。然后用DW（空白）或报警物质（AS）（对照，TBT低和TBT高）处理鱼。暴露后，使用镜检（镜咬频率，与接触试验的接近时间和进近区的持续时间）和斗鱼测试（咬鱼频率）与暴露于TBT的鱼相比，咬鱼的频率，接近镜子的时间，进近区的持续时间和咬鱼的频率与对照鱼的那些，表明攻击行为增强。在接受AS管理后，使用新型坦克下潜测试的TBT暴露鱼的恐惧反应参数（开始时间到上半部分，下半部分的总持续时间和翻转的频率）也显着增加，这表明恐惧反应有所增强。进一步的研究表明，TBT处理以浓度依赖的方式提高了11-酮睾酮（11-KT）的血浆水平，并降低了雌二醇（E2）的血浆水平。此外，TBT上调了ar的mRNA水平，c-fos和bdnf1，并抑制鱼中btg-2的表达。此外，暴露于AS会增加对照鱼和TBT处理鱼的5-HT合成相关基因（例如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。并抑制了btg-2在鱼类中的表达。此外，暴露于AS会增加对照鱼和TBT处理鱼的5-HT合成相关基因（例如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。并抑制了btg-2在鱼类中的表达。此外，暴露于AS会增加对照鱼和TBT处理鱼的5-HT合成相关基因（例如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，高TBT组中的AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。此外，暴露于AS会增加对照鱼和TBT处理鱼的5-HT合成相关基因（例如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。此外，暴露于AS会增加对照鱼和TBT处理鱼的5-HT合成相关基因（例如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。暴露于AS中会增加对照和TBT处理鱼中5-HT合成相关基因（如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。暴露于AS中会增加对照和TBT处理鱼中5-HT合成相关基因（如tph1b和pet1）的血浆皮质醇水平，并下调其mRNA表达水平。与对照鱼相比，在高TBT组中，AS显着抑制了tph1b，tph2，pet1和npy的mRNA水平。本研究表明，TBT可能通过改变血浆11-KT，E2和皮质醇水平以及改变参与攻击行为调节的基因（ar，c-fos，bdnf1和btg-2）和恐惧反应（tph1b，tph2，pet1和npy）。本研究极大地扩展了我们对TBT对鱼类行为毒性的理解。