Chronic Effects of Fluoxetine on Danio rerio: A Biochemical and Behavioral Perspective

Abstract

Fluoxetine is an antidepressant widely used to treat depressive and anxiety states. Due to its mode of action in the central nervous system (selective serotonin reuptake inhibitor (SSRI)), it becomes toxic to non-target organisms, leading to changes that are harmful to their survival. In this work, the effects of fluoxetine on juvenile zebrafish (Danio rerio) were evaluated, assessing biochemical (phase II biotransformation—glutathione S-transferase (GST), neurotransmission—acetylcholinesterase (ChE), energy metabolism—lactate dehydrogenase (LDH), and oxidative stress—glutathione peroxidase (GPx)) and behavior endpoints (swimming behavior, social behavior, and thigmotaxis) after 21 days exposure to 0 (control), 0.1, 1 and 10 µg/L. Biochemically, although chronic exposure did not induce significant effects on neurotransmission and energy metabolism, GPx activity was decreased after exposure to 10 µg/L of fluoxetine. At a behavioral level, exploratory and social behavior was not affected. However, changes in the swimming pattern of exposed fish were observed in light and dark periods (decreased locomotor activity). Overall, the data show that juvenile fish chronically exposed to fluoxetine may exhibit behavioral changes, affecting their ability to respond to environmental stressors and the interaction with other fish.

Effects of fluoxetine on fish: What do we know and where should we focus our efforts in the future?

“…For example, Chen et al (2018a) showed that in Pseudorasbora parva juveniles, a shortterm exposure (4 h) to 50 and 200 μg/L, resulted in CAT activity increase at the lowest concentration, while a chronic exposure (42 days) caused an inhibition at the highest concentration. Correia et al (2022) showed a decrease in GPx activity in juvenile D. rerio exposed for 21 days to 10 μg/L fluoxetine. Effects on the levels of the non-protein thiol with important role on non-enzymatic antioxidant defense, GSH has also been reported in Pseudorasbora parva juveniles exposed for 4 h to 50 μg/L fluoxetine, displaying an increase in hepatic GSH (153 %), at 200 μg/L.…”

“…Rapid light/dark changes have also been used for the assessment of stress responses. For example, Correia et al (2022) observed in D. rerio juveniles exposed to 1 and 10 μg/L Females followed less of their potential partners (all concentrations tested).…”

Personality Affects Zebrafish Response to Sertraline

“…Thoré et al (2020) reported that male Nothobranchius furzeri exposed to 5.3 µg/L of fluoxetine, another common SSRI, for 8 weeks displayed an increase in sociability by 34%, whereas Hong et al (2021) found that zebrafish exposed to high concentrations of sertraline, fluoxetine, and citalopram showed a decline in sociability after 21 days. In contrast, Correia et al (2022) concluded that fluoxetine did not alter the social behavior of zebrafish at a concentration ≥0.1 µg/L for 21 days.…”