Fish May Be More Sensitive to Antidepressants in Water Than Humans, Study Finds

Antidepressants and other drugs that target human brain chemistry remain biologically active after they leave the body, persisting in wastewater and eventually reaching rivers and seas. Because fish rely on the same neurotransmitters as humans — serotonin, dopamine and norepinephrine — these pharmaceuticals can interfere with fish behaviour and physiology too, though it has been unclear how sensitive fish are to them compared with humans, or whether that sensitivity is shared broadly across species.

A team led by Professor Shinichi Miyagawa of the Tokyo University of Science, with Professor Masaru Ihara of Kochi University, examined the monoamine transporters — proteins that clear serotonin, dopamine and norepinephrine from the gaps between nerve cells, and which antidepressants often target — in two evolutionarily distant fish species: medaka and ayu. The study was published on 24 August in Environmental Science & Technology.

The researchers cloned the genes for these transporters from both fish species, produced them in genetically engineered human cells, and exposed them to a range of commonly used antidepressants, measuring how strongly each drug blocked their activity. One version of the serotonin transporter, called SERTa, was consistently far more sensitive to antidepressants than a second version, SERTb — consistent with the human serotonin transporter belonging to the SERTa lineage, while SERTb does not exist in mammals.

Comparing fish SERTa with the human version, the researchers found the fish transporter often responded to lower drug concentrations, sometimes more than ten times lower than in humans, and that some drugs not typically thought to act on these proteins in humans still affected the fish versions. The concentrations needed to block fish SERTa overlapped with antidepressant levels already measured in polluted waterways: duloxetine, fluoxetine, citalopram and paroxetine inhibited medaka SERTa at concentrations from a few hundred to roughly 1,300 nanograms per litre.

"By demonstrating that key molecular targets in fish can be more sensitive than their human equivalents, our work offers crucial insights into the potential risks of pharmaceutical exposure to aquatic wildlife," said Professor Miyagawa, adding that the findings could help prioritise specific pharmaceuticals in environmental monitoring programmes.