Early antidepressant exposure rewrites the script of coping

Abstract

Exposure to neuropharmaceuticals at early stages of development may affect brain development and elicit long-lasting effects, leading to alterations in stress-coping behaviour, critical for adaptation in ecosystems progressively shaped by anthropogenic influences. Paroxetine (PAR), a selective serotonin reuptake inhibitor antidepressant, has been increasingly detected in water systems worldwide, raising concerns about its impact on biota, as it has been shown to affect fish behaviour. However, the effects of PAR exposure on stress-coping styles, such as the bold-shy scope and personality-linked behavioural responses, remain unexplored. Nevertheless, considering the role of behavioural variability in population adaptability, disruptions to these traits during brain development may have important ecological implications. Thus, this study aimed to assess how zebrafish's early developmental exposure to environmental levels of PAR may affect later-life stress-coping behaviours. To investigate this, zebrafish embryos were exposed during a susceptible developmental window (from 3 to 48 h post-fertilisation, hpf) to 0.04 and 0.4 µg/L PAR. After exposure, embryos were transferred to clean media and allowed to develop until the larval stage (8 days post-fertilisation, dpf) and the juvenile stage (45 dpf). Transient embryonic exposure to PAR disrupted the normal development of coping styles, with early behavioural alterations progressing into more pronounced, phenotype-specific disruptions in behaviour, monoaminergic and endocrine regulations at the juvenile stage.