Environmental concentration of fluoxetine disturbs larvae behavior and increases the defense response at molecular level in zebrafish (Danio rerio)

Fluoxetine (FLX) is one of the main antidepressants used worldwide. After human use, FLX enters the aquatic ecosystems, where it has commonly detected in the high ng/L concentration range. Several investigations have shown that exposure to different concentrations of FLX caused different adverse effects towards a number of aquatic species. However, the information on the onset and the relationship between molecular and behavioral FLX-induced effects remains scant. The aim of this study was to assess the effects induced by two FLX concentrations, namely 50 ng/L and 500 ng/L, on swimming activity of zebrafish (Danio rerio) larvae at 96-h post-fertilization (hpf) and to investigate if such behavioral effects were related to modulation of the expression of oxidative stress-related (sod1, sod2, cat, gpxa, and gst), stress- and anxiety-related (oxtl, prl2, npy, and ucn3l) genes, and genes encoding for the transporters of the main neurotransmitters (slc6a3, slc6a4a, slc6a4b, slc6a11). Fluoxetine exposure altered the swimming behavior of larvae, as shown by the reduction of the distance traveled by treated larvae in response to an external stimulus. Such behavioral change was related, at molecular level, to an enhanced expression of sod1, cat, and gpxa, suggesting an overproduction of pro-oxidant molecules. In addition, FLX modulated the expression of oxtl, slc6a4a, slc6a4b, and slc6a11, suggesting its capability to affect anxiety- and neurotransmitter-related genes.