Physiological endpoints for potential SSRI interactions in fish

Selective serotonin reuptake inhibitors (SSRIs) are among the pharmaceutical compounds frequently detected in sewage treatment plant effluents and surface waters, albeit at very low concentrations, and have therefore become a focus of interest as environmental pollutants. These neuroactive drugs are primarily used in the treatment of depression but have also found broader use as medication for other neurological dysfunctions, consequently resulting in a steady increase of prescriptions worldwide. SSRIs, via inhibition of the serotonin (5-hydroxytryptamine, 5-HT) reuptake mechanism, induce an increase in extracellular 5-HT concentration within the central nervous system of mammals. The phylogenetically ancient and highly conserved neurotransmitter and neurohormone 5-HT has been found in invertebrates and vertebrates, although its specific physiological role and mode of action is unknown for many species. Consequently, it is difficult to assess the impact of chronic SSRI exposure in the environment, especially in the aquatic ecosystem. In view of this, the current knowledge of the functions of 5-HT in fish physiology is reviewed and, via comparison to the physiological role and function of 5-HT in mammals, a characterization of the potential impact of chronic SSRI exposure on fish is provided. Moreover, the insight on the physiological function of 5-HT strongly suggests that the experimental approaches currently used are inadequate if not entirely improper for routine environmental risk assessment of pharmaceuticals (e.g., SSRIs), as relevant endpoints are not assessed or impossible to determine.