Exposure to amitriptyline disturbs behaviors in adult zebrafish and their offspring via altering neurotransmitter levels

Amitriptyline (AMI), one of the widely used tricyclic antidepressants (TCAs), has become a pharmaceutical contaminant frequently detected in aquatic ecosystems. However, the impacts of AMI exposure and underlying mechanisms on fish are still limited. In this study, adult zebrafish (F0) were exposed to AMI at 0 (control), 0.8, and 8 μg/L for 14 days. Subsequently, the exposed zebrafish were paired for spawning, and their offspring (F1) were reared in an AMI-free medium until 5 days post-fertilization (dpf). This study aimed to assess variations in behaviors and neurotransmitter levels in both the F0 (at the end of the 14-day exposure) and F1 generations (at 5 dpf). As a result, waterborne AMI exposure significantly reduced the locomotor activity, frequency of body contact, and duration of chase in F0 zebrafish, and resulted in notable changes in monoamine neurotransmitter levels in their brains. Parental exposure to AMI significantly elevated the heart rate and eye movement but reduced the locomotor activity in the F1 zebrafish, also along with significant changes in monoamine neurotransmitters and acetylcholine. Furthermore, significant correlations between the changes in behavioral traits and neurotransmitter levels were identified in both F0 and F1 generations. Our findings confirm the critical role of monoamine modulation in the neurobehavioral toxicity of AMI on zebrafish and their offspring, and emphasize the importance of paying attention to its multigenerational effects on fish.