Brown University, Department of Molecular and Cellular Biology and Biochemistry, Providence, RI 02912, United States.
Brown University, Department of Molecular and Cellular Biology and Biochemistry, Providence, RI 02912, United States.
Neurotoxicol Teratol. 2018 Sep-Oct;69:54-62. doi: 10.1016/j.ntt.2017.10.009. Epub 2017 Oct 31.
Antidepressants are used by a substantial number of women in their childbearing years. Treatment may continue during pregnancy, since untreated depression poses a risk to the mother and child. However, many antidepressants readily pass through the placental barrier to reach the fetus or may be ingested by the newborn via breastmilk. Little is known about the effects of antidepressants on brain development and subsequent behavior in young children. In the current study, we used zebrafish as a model system to examine the neurodevelopmental effects of three commonly prescribed antidepressants, sertraline, duloxetine and bupropion. Zebrafish were exposed to these antidepressants during development and were examined for changes in larval avoidance behavior, activity, social behaviors, and anxiety-related behaviors. The results show that antidepressants commonly affect larval swim speeds and resting, and differentially affect other behaviors depending upon the exposure period. Using cluster analysis profiling, we compared the obtained results to previous reports on behavioral defects induced by organophosphate pesticides. We found that the behavioral profiles induced by antidepressants and pesticides overlap, indicating a common mechanism of action. We conclude that developmental antidepressant exposures lead to specific behavioral changes in zebrafish larvae. At present, it is not known if antidepressants have similar effects in human development.
抗抑郁药在生育年龄段的女性中大量使用。由于未经治疗的抑郁症会对母亲和孩子造成风险，因此治疗可能会在怀孕期间继续进行。然而，许多抗抑郁药很容易穿过胎盘屏障到达胎儿，或者可能通过母乳被新生儿摄入。关于抗抑郁药对幼儿大脑发育和随后行为的影响知之甚少。在目前的研究中，我们使用斑马鱼作为模型系统，研究了三种常用抗抑郁药（舍曲林、度洛西汀和安非他酮）对神经发育的影响。在发育过程中，斑马鱼暴露于这些抗抑郁药下，观察其幼鱼回避行为、活动、社交行为和焦虑相关行为的变化。结果表明，抗抑郁药通常会影响幼鱼的游动速度和静止状态，并且根据暴露期的不同，对其他行为产生不同的影响。通过聚类分析分析，我们将获得的结果与有机磷农药引起的行为缺陷的先前报告进行了比较。我们发现，抗抑郁药和杀虫剂引起的行为特征重叠，表明存在共同的作用机制。我们得出结论，发育中的抗抑郁药暴露会导致斑马鱼幼鱼出现特定的行为变化。目前尚不清楚抗抑郁药在人类发育中是否具有类似的影响。
