Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio
Due to the high incidence of depression during childbearing, antidepressants such as fluoxetine (FLX) are highly prescribed during pregnancy, yet the risks to offspring are unknown. We report that a 6-day FLX exposure during early zebrafish development induces hypocortisolism for at least three generations. Gene expression analysis indicates that pathways controlling cortisol synthesis are altered in the descendants in the third generation. This FLX-induced low-cortisol phenotype is more prominent in males and is associated with significantly reduced exploratory behaviors for two generations. This is an important demonstration that, in an animal model, even a brief ancestral exposure to a common antidepressant modifies the stress response and critical coping behaviors for several generations.