Fish may be highly sensitive to antidepressants found in water. Many of the drugs that target human brain chemistry, such as antidepressants, remain biologically active after leaving the body. These substances can persist in wastewater and eventually end up in rivers, lakes, or the sea. Because fish use the same neurotransmitters as humans—including serotonin, dopamine, and norepinephrine—pharmaceuticals designed to interact with these chemicals in humans can also affect fish, potentially altering their behavior and physiology. A research team led by Professor Shinichi Miyagawa from the Department of Biological Science and Technology at Tokyo University of Science in Japan studied monoamine transporters in two distinct fish species: medaka and ayu. Their findings, published in Environmental Science & Technology on August 24, 2026, were co-authored by Professor Masaru Ihara from Kochi University. The study focused on how antidepressants interact with these transporters, which are proteins that help move neurotransmitters across nerve cells. The researchers identified and cloned genes responsible for DAT, NET, and two types of SERT (SERTa and SERTb) from both fish species. Using genetically modified human cells, they produced these transporters in the lab and exposed them to various antidepressants. By measuring how effectively the transporters took up a fluorescent marker, the team determined how strongly each drug inhibited their activity. The results showed that SERTa was significantly more sensitive to antidepressants than SERTb in both fish species. This aligns with genetic analysis showing that human SERT is similar to SERTa, while SERTb is not found in mammals. Additionally, SERTb had certain genetic differences that may affect how it interacts with drugs. Surprisingly, fish SERTa often responded to lower drug concentrations than human SERT—sometimes more than 10 times lower. Some drugs not typically thought to affect these proteins in humans still impacted the fish versions, suggesting possible side effects not predicted by human studies. The concentrations of antidepressants needed to block fish SERTa in the lab were similar to those found in polluted waterways, such as duloxetine, fluoxetine, citalopram, and paroxetine, which inhibited medaka SERTa at levels between a few hundred and 1,300 nanograms per liter. Professor Miyagawa emphasized that the study highlights the increased sensitivity of fish to antidepressants compared to humans, which could help identify risks to aquatic life. Because the research involved two distantly related fish species, the findings suggest this vulnerability may be widespread among aquatic organisms. The study could assist regulators in setting more protective water quality standards and prioritizing certain pharmaceuticals for environmental monitoring. Future research will need to explore how these molecular effects translate into real-world ecological impacts when considering realistic drug exposure levels and combinations.