Ancestral exposure to amitriptyline disrupts the behavior and gene expression in zebrafish F2 offspring

Amitriptyline (AMI), a commonly used tricyclic antidepressant, has been identified as a significant pharmaceutical contaminant in aquatic environments. Although parental exposure of zebrafish to AMI has been found to induce changes in the development, behavior, and gene expression of their F1 offspring, it is unclear whether such adverse effects will be further extended to subsequent generations. In the current study, we explored the effects of ancestral exposure to AMI at environmentally relevant concentrations (0 and 0.8 μg/L) on the early life stages of zebrafish F2 offspring. The results showed that ancestral exposure to AMI had no significant effect on the survival and development of the zebrafish F2 offspring. However, significant hyperactivity was observed in the F2 larvae in the ancestral AMI exposure group during the dark periods of a light-dark locomotion assay. Transcription analysis revealed that ancestral exposure to AMI significantly disrupted pathways associated with xenobiotic biodegradation and metabolism, as well as the metabolism of cofactors and vitamins. Furthermore, ancestral exposure to AMI significantly decreased the level of cytochrome P450 and the activity of glutathione S-transferase within the F2 larvae, which are critical enzymes involved in xenobiotic metabolism. These findings provide valuable insights into the multigenerational effects of AMI exposure in zebrafish, emphasizing the importance of assessing the risks posed by such pollutants to fish populations.