Fluoxetine modulates the transcription of genes involved in serotonin, dopamine and adrenergic signalling in zebrafish embryos

Chemosphere. 2018 Jan:191:954-961. doi: 10.1016/j.chemosphere.2017.10.100. Epub 2017 Oct 27.

Abstract

Neurotransmitters pathways in fish and mammals are phylogenetically conserved. Therefore, the environmental presence of psychopharmaceuticals, such as fluoxetine (FLU), are likely to interact with fish serotonergic, dopaminergic and adrenergic systems, affecting their response and associated biological functions. Hence, the present work aimed at evaluating the effects of FLU in the transcription of genes involved in serotonin, dopamine and adrenergic transporters and receptors signalling in early stages of Danio rerio development. Embryos (1 hpf) were exposed for 80 h to different concentrations of FLU (0.0015, 0.05, 0.1, 0.5 and 0.8 μM) and mRNA levels of sert, 5-ht1a, 5-ht2c, dat, drd1b, drd2b, net, adra2a, adra2b, adra2c, vmat and mao were evaluated. A sensorimotor reflex assay was also performed demonstrating a significant decrease in tail reflex at 0.1 and 0.5 μM. The transcription levels of serotonergic and dopaminergic transporters (sert and dat) and vmat were down-regulated at environmentally relevant concentration (0.0015 μM). Receptors 5-ht2c, drd2b adra2b and adra2c mRNA levels also displayed a down regulation pattern after FLU exposure. In conclusion, this study demonstrated the interaction of FLU with the neurotransmission system at environmentally relevant concentrations by changing transcription patterns. Therefore, given the importance of these signalling pathways it is possible that their disruption can ultimately disturb the escape behaviour and biological functions in fish. Hence, evaluating the presence of this psychopharmaceutical in the aquatic environment should be implemented in future monitoring programmes.

Keywords: Danio rerio embryos; Monoamine receptors and transporters; Psychopharmaceuticals; mRNA levels.

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Down-Regulation / drug effects
  • Embryo, Nonmammalian
  • Fluoxetine / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects*
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Sensorimotor Cortex / drug effects
  • Serotonin / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / genetics
  • Water Pollutants, Chemical / adverse effects*
  • Zebrafish / embryology
  • Zebrafish / metabolism

Substances

  • ADRA2B protein, human
  • Receptors, Adrenergic, alpha-2
  • Serotonin Uptake Inhibitors
  • Water Pollutants, Chemical
  • Fluoxetine
  • Serotonin
  • Dopamine