Personality Affects Zebrafish Response to Sertraline.

Sertraline is widely prescribed to treat anxiety and depression. Sertraline acts by blocking serotonin, norepinephrine, and dopamine transporters systems and has been detected in surface waters globally, where it may impact fish behavior. We classified zebrafish personality on three behavioral axes, boldness, anxiety, and sociability, assigning fish as either high or low in each category. The fish were exposed to nominal concentrations of 0, 5, 50, 500, or 5000 ng/L sertraline (measured concentrations: <10, 21.3, 370, and 2200 ng/L, respectively) to assess changes in boldness, anxiety, and sociability after 7 and 28 days. We also measured shoaling behavior and response to an alarm cue, and determined the gut microbiome of a subset of fish. After 7 days there was no overall effect of sertraline on boldness, but there was an interaction between initial personality and sex, with a stronger impact on females classified as low-boldness personality. Sertraline reduced sociability in all treatments compared with the control, but there was again an interaction between sertraline and initial personality. Fish that were classified as low-sociability responded more strongly to sertraline. After 7 days, fish exposed to a nominal concentration of 5000 ng/L (2200 ng/L measured) showed higher anxiety than controls, with the overall pattern of initial behavior retained. After 28 days, similar patterns were observed, but with higher variation. There was only a weak association between the gut microbiome and personality. Overall, the study highlights the importance of considering initial behavior, which can affect response to pollutants. Our results may also be applicable to human studies and provide a mechanism to explain why different individuals respond differently to the drug. Environ Toxicol Chem 2024;43:132-146. © 2023 SETAC.

Time-, dose- and transgenerational effects of fluoxetine on the behavioural responses of zebrafish to a conspecific alarm substance.

Despite publication of numerous of papers, the effects of fluoxetine on fish behaviour remains mired in controversy and contradiction. One reason for this controversy is that fluoxetine displays distinct and opposing acute and chronic effects. A second reason is that most studies have been limited to two or at the most three concentrations. To address these deficiencies we exposed adult zebrafish, both single females and shoals consisting of one male and two females, to seven fluoxetine concentrations, ranging from 5 ng/L to 5 µg/L and measured their swimming behaviour, and response to a conspecific alarm substance (CAS) at seven, 14 and 28 days. We also measured the light startle response of unexposed F1 larvae at days seven and 28 post-hatch and the response to CAS at day 28. On day 7 fluoxetine decreased swimming speed at concentrations ≥500 ng/L. After addition of CAS fish exposed to 5, 500 and 1000 ng/L decreased swimming, while fish exposed to 10, 500 and 1000 ng/L significantly increased time motionless. On day 14 only fish exposed to 50 ng/L were significantly slower than controls before addition of CAS, but afterwards fish exposed to 5, 50, 1000 and 5000 ng/L showed significant differences from controls. On day 28 fish exposed to 50 and 5000 ng/L had slower average swimming speeds than controls before addition of CAS. After addition all fish except controls and those exposed to 500 ng/L showed decreased average speed. At seven days post-hatch, F1 larvae whose parents were exposed to 100 ng/L showed significantly higher activity than controls and those exposed to 500 ng/L fluoxetine showed lower activity in the light startle response. This study shows that the effects of fluoxetine vary with time and also in a non-monotonic manner. We suggest that the complex nature of the serotonergic system with multilateral effects at the genomic, biochemical and physiological levels interacting with environmental stimuli result in non-linear dose-response behavioural patterns.