Combinatory effects of low concentrations of 17α-etinylestradiol and citalopram on non-reproductive behavior in adult zebrafish (Danio rerio)

Abstract

Sewage effluents contain pharmaceuticals, personal care products and industrial chemicals, exposing aquatic organisms to complex mixtures. The consequences of exposure to combinations of different classes of drugs in fish are largely unknown. In this study, we exposed adult zebrafish (Danio rerio) males and females for two weeks to low, environmentally relevant concentrations of the endocrine disrupting chemical 17α-etinylestradiol (EE) and the selective serotonin re-uptake inhibitor (SSRI) citalopram, alone and in combination, and analyzed behaviors of importance for population fitness, scototaxis (light/dark preference), the novel tank test and shoal cohesion. Control water contained 0.4ng/L EE and the measured exposure concentrations were 0.9ng/L EE (nominal 0.1) and 1ng/L EE (nominal 0.5). The measured concentrations of citalopram were 0.1 (nominal 0.1) and 0.4μg/L (nominal 0.5). Both EE exposures increased anxiety in males in the scototaxis test, with significantly longer latency periods before entering and fewer visits to the white zone of the tank. The combined exposures (0.9ng/L EE+0.1μg/L citalopram and 1ng/L EE+0.4μg/L citalopram) resulted in abolishment of effects of EE, with shorter latency period and more transitions to white than for fish exposed to EE alone. In the novel tank test, the results surprisingly indicated lower anxiety after both EE and citalopram exposure. Significantly more transitions to the upper half of the tank observed in males exposed to 0.1μg/L citalopram alone compared to control males. Males exposed to EE (0.9ng/L) had shorter latency period to the upper half. Combination exposure resulted in a longer latency and fewer transitions to the upper half compared to both control, EE- and citalopram-exposed males. Males exposed to the combination spent significantly less time in the upper half than males EE or citalopram-exposed males. Females exposed to 1ng/L EE had fewer transitions to the upper half than the control group and females exposed to 0.4μg/L citalopram. In the shoaling test, males exposed to 0.1μg/L citalopram+0.9ng/L EE showed more transitions away from peers than males exposed to 0.1μg/L citalopram alone. In conclusion, low concentrations of EE, closely above the predicted no effect concentration (NOEC) of 0.1ng/L, created anxiety-like behavior in zebrafish males. Citalopram showed marginal effects at these low concentrations but in the combination exposure the behavioral effects of EE were abolished. This is an initial effort to understand the effects of cocktails of anthropogenic substances contaminating aquatic environments.

Mycotoxin zearalenone induced gonadal impairment and altered gene expression in the hypothalamic–pituitary–gonadal axis of adult female zebrafish (Danio rerio)

“…Similarly, the non-monotonous gene expression of HPG axis were also reported for 17α-etinylestradiol and citalopram (Porseryd et al, 2017) and Tris (1,3-dichloro-2-propyl) phosphate and triphenyl phosphate treated zebrafish. Aromatase enzyme (CYP19) is responsible for catalyzing the final conversion of testosterone to estradiol, which is essential for the HPG axis involved in the adult reproductive process (Naderi et al, 2014).…”

Effects of pharmaceutically active compounds (PhACs) on fish body and scale shape in natural waters

“…CITA as a SSRI, have also been shown to significantly affect roach body shape. A strong anxiolytic effect has been reported in fish previously (Olsén et al, 2014;Porseryd et al, 2017), and alterations in behavioral patterns might also affect the phenotype as well, because the use of different habitats might alter the phenotype of different species (Faulks et al, 2015). CODE an opiate derivative, is used to treat rheumatic pain (Ytterberg, Mahowald & Woods, 1998), and significantly modulates chub-scale shape.…”

Effects of the Antidepressants Citalopram and Venlafaxine on the Big Ramshorn Snail (Planorbarius corneus)

“…However, concentrations of up to 1 µg/L Venlafaxine were found in effluents of wastewater treatment plants and for citalopram concentrations up to 76 µg/L were found in Indian rivers [12][13][14]. For both antidepressants, adverse effects in aquatic organisms have been observed, with the majority of studies addressing behavioural effects in fish [15][16][17][18][19][20][21][22][23]. Regarding biochemical or histological endpoints, only a couple of studies have been conducted [24][25][26][27].…”