Proximate causes and ultimate effects of common antidepressants, fluoxetine and venlafaxine, on fish behavior

Antidepressant (AD) drugs are widely prescribed for the treatment of psychiatric disorders, including depression and anxiety disorders. The continuous use of ADs causes significant quantities of these bioactive chemicals to enter the aquatic ecosystems mainly through wastewater effluent discharge. This may result in many aquatic organisms being inadvertently affected by these drugs. Fluoxetine (FLX) and venlafaxine (VEN) are currently among the most widely detected ADs in aquatic systems. A growing body of experimental evidence demonstrates that FLX and VEN have a substantial capacity to induce neurotoxicity and cause behavioral dysfunctions in a wide range of teleost species. At the same time, these studies often report seemingly contradictory results that are confounding in nature. Hence, we clearly require comprehensive reviews that attempt to find overarching patterns and establish possible causes for these variable results. This review aims to explore the current state of knowledge regarding the neurobehavioral effects of FLX and VEN on fishes. This study also discusses the potential mechanistic linkage between the neurotoxicity of ADs and behavioral dysfunction and identifies key knowledge gaps and areas for future research.