Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. In this study we have used a behavioural platform in a phenotypic screen to identify drugs that can reduce zebrafish aggression without affecting locomotion. In a three tier screen of ninety-four drugs we discovered that caffeine and sildenafil can selectively reduce aggression. Caffeine also decreased attention and increased impulsivity in the 5-choice serial reaction time task whereas sildenafil showed the opposite effect. Imaging studies revealed that both caffeine and sildenafil are active in the zebrafish brain, with prominent activation of the thalamus and cerebellum evident. They also interact with 5-HT neurotransmitter signalling. In summary, we have demonstrated that juvenile zebrafish are a suitable model to screen for novel drugs to reduce aggression, with the potential to uncover the neural circuits and signalling pathways that mediate such behavioural effects.

中文翻译：

---

筛选减少斑马鱼攻击性的药物可识别咖啡因和西地那非

虽然攻击性是精神疾病的常见症状，但可用于治疗它的药物是非特异性的，可能会产生不必要的副作用。在这项研究中，我们在表型筛选中使用了一个行为平台来识别可以减少斑马鱼攻击而不影响运动的药物。在包含 94 种药物的三层筛选中，我们发现咖啡因和西地那非可以选择性地减少攻击性。在 5 项选择系列反应时间任务中，咖啡因还降低了注意力并增加了冲动性，而西地那非则显示出相反的效果。成像研究表明，咖啡因和西地那非在斑马鱼大脑中都很活跃，丘脑和小脑的显着激活是显而易见的。它们还与 5-HT 神经递质信号相互作用。总之，