Prescribed aggression of fishes: Pharmaceuticals modify aggression in environmentally relevant concentrations

Abstract

Traces of psychoactive substances have been found in freshwaters globally. Fish are chronically exposed to pollution at low concentrations. The changes of aggressive behaviour of chub (Squalius cephalus) were determined under the exposure to four psychoactive compounds (sertraline, citalopram, tramadol, methamphetamine) at environmentally relevant concentrations of 1 μg/L for 42 days. We tested whether (A) the behavioural effect of compounds varies within a single species; (B) there is a correlation between the individual brain concentration of the tested pollutants and fish aggression using the novel analysis of pollutants in brain; and (C) there is detectable threshold to effective pollutant concentration in brain. Behaviour and pollutant concentrations in brain were determined repeatedly (1st, 7th, 21st, 42nd and 56th days), including a two-week-long depuration period. The effect of particular compounds varied. Citalopram and methamphetamine generally increased the fish aggression, while no such effect was found after exposure to tramadol or sertraline. The longitudinal analysis showed an aggression increase after depuration, indicating the presence of withdrawal effects in methamphetamine- and tramadol-exposed fish. The analysis of pollutant concentration in brain revealed a positive linear relationship of citalopram concentration and aggression, while no such effect was detected for other compounds and/or their metabolites. Structural break analyses detected concentration thresholds of citalopram (1 and 3 ng/g) and sertraline (1000 ng/g) in brain tissue, from which a significant effect on behaviour was manifested. While the effect of sertraline was not detected using traditional approaches, there was a reduction in aggression after considering its threshold concentration in the brain. Our results suggest that pursuing the concentration threshold of psychoactive compounds can help to reduce false negative results and provide more realistic predictions on behavioural outcomes in freshwater environments, especially in the case of compounds with bioaccumulation potential such as sertraline.

Keywords: Citalopram; Methamphetamine; Pharmaceuticals; Sertraline; Tramadol; Withdrawal effects.