Sex-Specific and Long-Term Impacts of Early-Life Venlafaxine Exposure in Zebrafish

Abstract

Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is a widely prescribed antidepressant that is detected in municipal wastewater effluents at µg/L concentrations. It has been shown to impact the early life stages of fish, including neurodevelopment and behaviour in larvae, but whether such early exposures have longer-term consequences are far from clear. Here, we sought to determine whether zygotic deposition of venlafaxine, mimicking a maternal transfer scenario, disturbs the metabolic rate and behavioural performance using zebrafish (Danio rerio). This was tested using freshly fertilized embryos (1–4 cell stage) microinjected with either 0, 1 or 10 ng of venlafaxine and raised to either juvenile (60 days post-fertilization) or adult (10–12 months post-fertilization). Zygotic venlafaxine exposure led to a reduction in the active metabolic rate and aerobic scope, but this was only observed in female fish. On the other hand, the total distance travelled in an open field assessment was greater at the highest concentration of venlafaxine only in the adult males. At the juvenile stage, behavioural assessments demonstrated that venlafaxine exposure may increase boldness—including hyperactivity, lower thigmotaxis, and a reduction in the distance to a novel object. Taken together, these results demonstrate that zygotic venlafaxine exposure may impact developmental programming in a sex-specific manner in fish.