Abstract:

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety, depressive and affective disorders. SSRIs enter the aquatic environment due to insufficient wastewater treatment, exposing non-target species. Adult male zebrafish (Danio rerio) exposed to Fluoxetine (FLX; Prozac) during early development exhibit reduced exploratory behaviour and hypocortisolism, as did their offspring over three generations. Developmental exposure to FLX causes life-long dysregulation of pathways involved in nervous system development, stress response, and lipid metabolism. In this study, we characterized the effects of different SSRIs: FLX, Citalopram (CIT; Celexa), and Escitalopram (ECIT; Cipralex), at environmental and pharmacological concentrations. We used the stress-responsive SR4G (Stress Responsive 4h half-life eGFP) transgenic zebrafish reporter line, with a cortisol-inducible enhanced green fluorescent protein (eGFP). After exposure for six days post-fertilization, larvae undergo a standardized net-handling stress protocol, to assess the effects of SSRIs on whole-body cortisol and eGFP mRNA levels. This study provides essential data to establish eGFP expression as an amenable and reliable biomarker of cortisol responses. Untreated larvae in stressed conditions presented a significant increase in whole-body cortisol and eGFP expression, compared to unstressed conditions. We detected a similar stress response in larvae exposed to FLX, CIT and ECIT, suggesting no effect of SSRIs on the stress axis under the applied experimental conditions of this study. However, positive correlation coefficients (0.82