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Updated: Oct 1, 2025
Behavioral Approaches to Studying Innate Stress in Zebrafish
Published on: May 1, 2019
Persistent impact of amitriptyline on the behavior, brain neurotransmitter, and transcriptional profile of zebrafish
Xuchun Qiu1, Chen Chen2, Yanhong Shi2
1Institute of Environmental Health and Ecological Security, School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Laboratory of Marine Environmental Science, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan; Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment, Suzhou University of Science and Technology, Suzhou 215009, China.
Abstract:
Discontinuation of amitriptyline (AMI) has been demonstrated to induce long-term withdrawal syndromes in mammals. However, no studies have focused on the persistent impacts of short-term AMI exposure on teleosts. Here, following exposure to AMI (2.5 and 40 μg/L) for 7 days (E7), zebrafish were transferred into AMI-free water to recover for 21 days (R21). The behavior, brain neurotransmitters, and brain transcriptional profiles were investigated on E7 and R21. AMI exposure induced persistent hypoactivity (2.5 and 40 μg/L) and abnormal schooling behavior (40 μg/L). AMI also induced long-term impacts on the brain serotonin (5-HT), 5-hydroxyindoleacetic acid, norepinephrine, and acetylcholine levels, several of which showed significant correlations with the locomotor activity or schooling behavior. Transcriptional analysis revealed persistent dysregulation in the pathways involved in the circadian rhythm, glycan biosynthesis and metabolism, and axon guidance in brain samples. Twelve genes were predicted as key driver genes in response to AMI exposure, and their significantly differential expression may direct changes across the related molecular networks. Moreover, upregulated brain 5-HT may serve as the central modulator of the persistent AMI pathogenesis in zebrafish. Considering AMI residues in natural waters may temporarily exceed μg/L, corresponding persistent adverse effects on teleosts should not be ignored.
