Environmentally relevant concentrations of antidepressant mirtazapine impair the neurodevelopment of zebrafish (Danio rerio)

Mirtazapine is a commonly prescribed antidepressant and has been found widespread in aquatic environments. However, its toxicities to aquatic organisms has rarely been explored. Herein, we conducted a comprehensive study on the developmental effects of mirtazapine on early life stages of zebrafish at environmentally relevant concentrations (3.9 ng/L and 43.5 ng/L). Out of the endpoints measured, spontaneous contraction of embryos at 24 h post fertilization (hpf) and hatching rate and heart rate of embryos at 50 hpf and 56 hpf, respectively, were significantly affected. In light-dark transition behavior test, mirtazapine significantly reduced the swimming frequency and swimming speed of embryos at both concentrations of 3.9 ng/L and 43.5 ng/L. Furthermore, the total swimming distances in dark conditions were also significantly reduced. Transcriptomic analysis was further conducted. It demonstrated that the decreased neural activities in embryos may be associated with altered epinephrine and neuregulin signaling. The present results fill a data gap regarding the exposure of fish to mirtazapine at environmentally relevant concentrations and provide new insights into the neurotoxic mechanisms of mirtazapine exposure.