The pyrethroid esfenvalerate induces hypoactivity and decreases dopamine transporter expression in embryonic/larval...

Esfenvalerate is a pyrethroid insecticide used widely for agricultural and residential applications. This insecticide has been detected in aquatic environments at concentrations that can induce sub-lethal effects in organisms. In this study, zebrafish embryos were used to examine the effects of environmentally-relevant concentrations of esfenvalerate on development and behavior. It was hypothesized that esfenvalerate exposure would impair locomotion due to its effects on the central nervous system. We also measured mitochondrial bioenergetics and the expression of genes (dopamine system) as putative mechanisms of locomotor impairment. Concentrations of 0.02, 0.2 and 2 μg/L esfenvalerate did not induce significant mortality nor deformity in zebrafish, but there was an acceleration in hatching time for zebrafish exposed to 2 μg/L esfenvalerate. As an indicator of neurotoxicity, the Visual Motor Response (VMR) test was conducted with 5, 6, and 7 dpf zebrafish after continuous exposure, and higher concentrations were used (4 and 8 μg/L esfenvalerate) to better discern age-and dose dependent responses in behavior. Experiments revealed that, unlike the other stages, 6 dpf larvae showed evidence for hypo-activity with esfenvalerate, suggesting that different stages of larval development may show increased sensitivity to pyrethroid exposure. This may be related to age-dependent maturation of the central nervous system. We hypothesized that reduced larval activity may be associated with impaired production of ATP and the function of mitochondria at earlier life stages, however dramatic alterations in oxidative phosphorylation were not observed. Based on evidence that dopamine regulates behavior and studies showing that other pyrethroids affect dopamine system, we measured transcripts involved in dopaminergic signaling. We found that dopamine active transporter was down-regulated with 0.2 μg/L esfenvalerate. Lastly, we comprehensively summarize the current literature (>20 studies) regarding the toxicity of pyrethroids in zebrafish, which is a valuable resource to those studying these pesticides. This study demonstrates that esfenvalerate at environmentally-relevant levels induces hypoactivity that are dependent upon the age of the zebrafish, and these behavioral changes are hypothesized to be related to impaired dopamine signaling.