Caffeine-induced bradycardia, death, and anxiety-like behavior in zebrafish larvae
Caffeine-induced bradycardia, death, and anxiety-like behavior in zebrafish larvae
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DOI：
10.1007/s11419-021-00577-8
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发表时间：
2021-04-24
影响因子：
2.2
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
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作者：
Maeda, Hideyuki;Hasumi, Akihiro;Yoshida, Ken-ichi
咖啡因是咖啡和其他饮料的主要成分，对健康的影响很小。然而，过量摄入咖啡因可能会诱发情绪和心脏事件。对斑马鱼幼虫的研究被认为有助于了解药物中毒，因为它们可以用于多种模拟。方法采用光暗试验和自动视频跟踪系统，测定不同浓度咖啡因对斑马鱼幼鱼游动距离的影响。死亡率和心率分别在暴露于咖啡因后4和24小时以及去除咖啡因后24小时进行评估。结果> 300 mg/L的咖啡因暴露24 h后，心脏率和存活率呈剂量依赖性降低，4 h后去除咖啡因可减轻心脏率和存活率。咖啡因在1000 mg/L时显著降低心率和存活率，支持咖啡因诱导心动过缓导致心脏骤停的概念。在6个交替周期的光-暗暴露的斑马鱼幼虫的运动是在光周期较慢，在黑暗期间较快; 100-300 mg/L的咖啡因增加和减少运动在光和黑暗周期，分别与高周期间的重现性。结论考虑到咖啡因的焦虑效应和斑马鱼幼鱼的光偏好性，咖啡因诱导的光暗周期变化可能为焦虑提供一个新的可靠的标记。因此，本研究所采用的“明-暗运动试验”对研究致焦虑或抗焦虑物质具有一定的参考价值。该测试可以允许在多种条件下同时和自动分析许多鱼的运动，从而能够评估咖啡因的剂量反应效应。
Purpose Caffeine, a major ingredient of coffee and other drinks, causes minimal health problems. However, excessive caffeine intake may induce emotional and cardiac events. Studies on zebrafish larvae are considered useful for understanding drug poisoning because they can be used for multiple simulations. Methods The locomotion (swim distance) of zebrafish larvae exposed to varying concentrations of caffeine was measured using a light-dark test and an automatic video-tracking system. Mortality and heart rates were assessed 4 and 24 h after caffeine exposure and 24 h after caffeine removal. Results The heart and survival rates were reduced by exposure to caffeine of > 300 mg/L after 24 h in a dose-dependent manner; this was attenuated by caffeine removal at 4 h. Caffeine reduced the heart rate and survival considerably at 1000 mg/L, supporting the notion of caffeine-induced cardiac arrest resulting from bradycardia. The locomotion of zebrafish larvae during six alternating cycles of light-dark exposure was slower during light periods and faster during dark periods; 100-300 mg/L caffeine increased and decreased locomotion during light and dark cycles, respectively, with high inter-cycle reproducibility. Conclusions Given the anxiogenic effect of caffeine and light preference of zebrafish larvae, caffeine-induced changes in light-dark cycles could provide a new reliable marker for anxiety. Therefore, the "light-dark locomotion test" employed in this study is valuable for research on anxiogenic or anxiolytic substances. The test may allow simultaneous and automatic analysis of the locomotion of many fish under multiple conditions, thereby enabling evaluation of dose-response effects of caffeine.