Disruptive ecotoxicological effects of fluoxetine on serotoninergic signaling and enteric neurogenesis in early zebrafish larvae (Danio rerio)

This study investigated the multilevel effects of environmentally relevant concentrations of fluoxetine on serotonergic signaling and enteric neurogenesis in early zebrafish larvae (Danio rerio). To this end, zebrafish were exposed to various concentrations of fluoxetine for four days, from the 1,000-cell stage to 4 days post-fertilization (dpf).Following exposure, whole larvae were subjected to molecular, morphological, and behavioral analyses. All tested concentrations led to upregulation of the serotonin transporter (slc6a4a). At intermediate concentrations, overexpression of the serotonin receptor htr1aa was observed. The highest concentration caused a reduced total enteric neurons density, while the intermediate concentration reduced the density of serotonergic enteric neurons. Additionally, the highest concentration decreased larval locomotion and impaired their ability to differentiate between light and dark phases.Across all tested concentrations, fluoxetine disrupted serotonergic signaling, impaired enteric neurogenesis, and induced sedative-like behavioral effects.