Zebrafish (Danio rerio) larvae show behavioral and embryonic development defects when exposed to opioids at embryo stage.
Zebrafish (Danio rerio) larvae show behavioral and embryonic development defects when exposed to opioids at embryo stage.
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DOI：
10.1016/j.ntt.2021.106964
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发表时间：
2021-05
影响因子：
2.9
通讯作者：
Marrs JA
中科院分区：
文献类型：
--
作者：
Sales Cadena MR;Cadena PG;Watson MR;Sarmah S;Boehm Ii SL;Marrs JA
阿片类药物滥用继续困扰着社会，近年来已成为一种流行病，导致成瘾和死亡人数增加。目前尚不清楚产前阿片类药物使用如何影响儿童的生活。这项工作的目的是评估早期胚胎暴露于可待因或吗啡对斑马鱼（Danio rerio）的影响，检查原肠胚形成进程（表观代谢）、致畸效应、死亡率和运动行为对光/暗周期的反应。斑马鱼胚胎在受精后3至24小时（hpf）或3至48 hpf（分别为- 24或- 48）暴露于1、5或10 mg/L（分别为01、05或10）的可待因或吗啡（指定为C或M）。C10-24、C01-48、C05-48和C10-48组幼虫在受精后7 d （dpf）眼显著小于对照。光照/黑暗周期对照幼虫的运动行为表现为在黑暗周期中游泳时间和游泳距离更长。两天的可待因暴露产生了强烈的影响，由于移动距离的明暗循环，没有显示出显著的反应。吗啡暴露组表现出与2天可待因暴露组相似的效果，表现出较小的运动活动，并且在光/暗周期的非活动时间之间也没有显著差异。总之，我们观察到低致畸效应和死亡率效应。在黑暗时期，与对照组相比，暴露于高水平和较长时间的阿片类药物的动物活性较低。未来的研究将需要了解产生行为改变的神经缺陷。
Opioid abuse continues to plague society, and in recent years, there has been an epidemic, leading to increased addiction and death. It is poorly understood how prenatal opioid use affects the lives of children. The aim of this work was to evaluate the effect of early embryonic codeine or morphine exposure in zebrafish (Danio rerio), examining gastrulation progression (epiboly), teratogenic effects, mortality and locomotor behavior response to light/dark cycles. Zebrafish embryos were exposed to codeine or morphine (designated C or M) at 1, 5 or 10 mg/L (designated 01, 05 or 10, respectively) from 3 to 24 hours postfertilization (hpf) or from 3 to 48 hpf (designated −24 or −48 for 1 or 2 days of exposure, respectively). The C10–24, C01–48, C05–48 and C10–48 groups showed significantly smaller eyes than control larvae at 7 days postfertilization (dpf). Locomotor behavior of control larvae in light/dark cycles showed greater swimming time and distance in dark cycles. Two-day codeine exposure produced strong effects, showing no significant response due to light/dark cycles in distance moved. Morphine exposed groups showed similar effects as observed in 2-day codeine exposed groups, showing less large movement activity and also no significant difference between inactive duration in response to light/dark cycles. In conclusion, we observed low teratogenic effects and mortality effects. Animals exposed to high levels and higher exposure times of opioids were hypoactive, relative to controls, in the dark period. Future studies will be needed to understand the neural defects producing behavior changes.
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