Ames_2026_Aquat.Toxicol_301_108042

Antidepressants are among the most widely prescribed pharmaceuticals worldwide, and compounds such as sertraline and citalopram have been detected in surface waters, raising concerns about their impacts on non-target aquatic organisms. The current study aimed to (i) evaluate immediate behavioral responses to citalopram and sertraline using habitat selection (avoidance and colonization) in zebrafish (Danio rerio) under non-forced exposure, and (ii) integrate these responses with short-term biochemical and behavioral alterations after forced exposure. Concentrations tested were 0.05, 0.2, 1, and 15 microg/L for citalopram and 0.05, 0.1, 0.5, and 2 microg/L for sertraline. In non-forced exposure, fish underwent individual avoidance/colonization tests (5 min) and a population avoidance test (3 h); In forced exposure, fish were exposed for 48 h to each concentration to assess behavioral and biochemical biomarkers. Under non-forced exposure, the zebrafish population avoided all tested concentrations, preferring the least contaminated compartments (p < 0.05). Forced exposure induced predatory inhibition (citalopram: 0.05 and 1 microg/L; sertraline: 0.5-2 microg/L; p < 0.05), hypolocomotion (citalopram: 0.2-1 microg/L; sertraline: 0.5 microg/L; p < 0.05), and anxiety-like responses (citalopram: 15 microg/L; sertraline: 2 microg/L; p < 0.05); only sertraline increased aggressive behavior (0.1-2 microg/L, p < 0.01). Both antidepressants significantly increased antioxidant defenses, with Glutathione S-transferase and Catalase the most sensitive biomarkers, responding from 0.05 microg/L (citalopram) and 0.1 microg/L (sertraline), depending on tissue (p < 0.05). Acetylcholinesterase activity was altered at similar concentrations (p < 0.05). Integrating non-forced habitat selection with forced-exposure biomarkers revealed both contaminant avoidance and latent toxicity not be captured by conventional single-compartment assays.