Cluster analysis profiling of behaviors in zebrafish larvae treated with antidepressants and pesticides

Abstract 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.