Agradecimentos: The authors thank the Brazilian Federal District Research Support Foundation (FAPDF 06/2016) for the scholarships provided, the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES), and the Brazilian São Paulo Research Foundation (FAPESP 2018/03108-0) for supporting RARV, ACO/RARV and RO, respectively. We are also grateful to Juliana Bezerra de Melo Fix Vieira for technical assistance. This study was funded by grants from the Brazilian National Council for Scientific and Technological Development (CNPq 304209/2019-8) to CKG; and supported by the Centre for Environmental and Marine Studies (CESAM, UID/AMB/50017/2019, Portugal), FCT/MCTES through national funds to ID Ver menos

Abstract: Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006-500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to = 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario Ver menos