Ancestral fluoxetine exposure sensitizes zebrafish to venlafaxine-induced reductions in cortisol and spawning. - GreenMedInfo Summary

Due to the prevalence of depression during childbearing, mothers may be prescribed multiple antidepressants, yet little is known about the risk and consequences to the offspring or to the subsequent generations. Fluoxetine (FLX) is usually the first line of pharmacological treatment for affective disorders in pregnant women, and venlafaxine (VEN) may be used as a secondary treatment. Given that FLX and VEN readily cross the placenta, a fetus from a treated pregnant woman is potentially at risk from the endocrine disruptive effects of these chemicals. Pharmaceuticals including FLX and VEN reach aquatic ecosystems through sewage release, so fish may be inadvertently affected. Here, we report that a 6-day FLX exposure during early zebrafish development to an environmentally relevant (0.54µg·L-1 in water) and a concentration detected in the cord blood of FLX-treated pregnant women (54 µg·L-1 in water) reduces the stress response (the arithmetic difference between the stress-induced and unstressed whole-body cortisol levels) in the adult females and males, an effect that persistsfor four generations. To model the possibility of a second antidepressant exposure, the filial generation 4 (F4), was exposed to VEN (5 µg·L-1). We found that FLX exposure sensitizes these descendants to VEN. The VEN treatment further suppresses cortisol production in females and decreases spawning rates in adult pairs. This is an important demonstration that in an animal model, a brief ancestral exposure of great-great-grandparents to the selective serotonin reuptake inhibitor FLX shapes the physiological responses of future generations to the serotonin and norepinephrine reuptake inhibitorVEN.