Transcriptional analyses reveal different mechanism of toxicity for a chronic exposure to fluoxetine and venlafaxine on the brain of the marine fish Dicentrarchrus labrax.

Selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitor (SNRI) are prescribed for clinical depression and detected in aquatic ecosystems. The main aim of this study was to explore and evaluate transcriptional responses of neurotransmitter genes in the brain of a marine fish species, European seabass, and to analyze global brain transcriptomic changes by a RNA-seq technology (MACE, massive analysis of cDNA ends). The juveniles were exposed to two psychopharmaceuticals: (i) fluoxetine (FLX) at the concentration of 0.5 μg/L and 50 μg/L; (ii) venlafaxine (VENX) at the concentration of 0.01 μg/L and 1 μg/L. The exposures were performed for 21 days, followed by a 7-day recovery period to assess the reversibility of effects. Both psychopharmaceuticals affected differentially the neurotransmitter mRNA expression analyzed by RT-qPCR (serotonin receptors: 5-ht3a, 5-ht3b; dopamine receptors: d2, d3; neurotransmitter transporter: sert, vmat; degrading enzyme: mao). Transcriptomic analyses after 21 days of exposure revealed 689 and 632 significant different transcripts by FLX at 0.5 and 50 μg/L, respectively, and 432 and 1250 by VENX at 0.01 and 1 μg/L, respectively, and confirmed different mechanism of toxicity between both compounds. At environmental concentrations, more general pathways including energy metabolism were affected, while at the higher concentration effects on neurotransmitter pathways were observed (FLX: exocytosis and vesicle formation; VENX: small molecule catabolism regulating dopamine and tyrosine level). These results provided new insights into the chronic effects of psychopharmaceutical compounds on marine fish and suggest the need of a separate ecotoxicological risk analysis.