利用行為組學進行抗憂鬱藥物對斑馬魚運動活力的評價

Evaluation of the Locomotor Performance in Zebrafish after Exposed to Antidepressants by Phenomic Approach

蘇麥克(Michael Edbert Suryanto)

指導教授 ： 蕭崇德

中原大學/理學院/生物科技研究所/碩士(2021年)

https://doi.org/10.6840/cycu202100699

摘要

抗抑鬱藥是治療人類抑鬱的精神藥物。然而，抗抑鬱藥的濫用與誘發的相關副作用的相關報導不斷增加。本研究的目的是通過監測斑馬魚幼魚的運動活性，來評估18種常見抗抑鬱藥的潛在不良反應。實驗方法是利用Zebrabox儀器檢測斑馬魚胚胎在明暗交替週期變化環境中，展現的行進的總距離，爆發運動計數和總旋轉計數來進行評價。通常，斑馬魚幼魚在抗抑鬱劑暴露後，所有與運動相關的評價指標均顯著降低(顯示出鎮靜作用)。但是，我們發現其中有三種抗抑鬱藥，即amitriptyline， amoxapine與sertraline能明顯觸發斑馬魚幼魚展現較高的自發活動。這些差異可能是由於抗抑鬱藥之間的藥理差異所致。另外，由於每種抗抑鬱藥具有彼此不同的劑量範圍，因此過量服用這些抗抑鬱藥也可能是造成這些差異的原因。基於這些結果，我們進一步觀察這三種抗抑鬱藥在較低濃度下的作用。結果表明三種抗抑鬱藥在斑馬魚幼魚運動能力方面展現出雙相效應 (低濃度促進，但是高濃度抑制)。這些發現表明這三種抗抑鬱藥可能共享一個共同的機制，來影響其對斑馬魚幼魚運動能力。

關鍵字

斑馬魚 ； 抗抑鬱藥 ； 行為 ； 運動 ； 雙相效應

並列摘要

Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larvae locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.

並列關鍵字

zebrafish ； antidepressants ； behavior ； locomotion ； biphasic effect

參考文獻

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