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.

已证明停用阿米替林 (AMI) 会导致哺乳动物出现长期戒断综合征。然而，没有研究关注短期 AMI 暴露对硬骨鱼的持续影响。在这里，在暴露于 AMI（2.5 和 40 μg/L）7 天后（E7），斑马鱼被转移到无 AMI 的水中恢复 21 天（R21）。在 E7 和 R21 上研究了行为、脑神经递质和脑转录谱。AMI 暴露导致持续性活动减退（2.5 和 40 μg/L）和异常的学校教育行为（40 μg/L）。AMI 还对大脑血清素 (5-HT)、5-羟基吲哚乙酸、去甲肾上腺素和乙酰胆碱水平产生长期影响，其中一些与运动活动或学习行为显着相关。转录分析显示脑样本中涉及昼夜节律、聚糖生物合成和代谢以及轴突引导的通路持续失调。12 个基因被预测为响应 AMI 暴露的关键驱动基因，它们的显着差异表达可能指导相关分子网络的变化。此外，上调的脑 5-HT 可作为斑马鱼持续性 AMI 发病机制的中枢调节剂。考虑到天然水中的 AMI 残留量可能暂时超过微克/升，因此不应忽视对硬骨鱼的相应持续性不利影响。它们的显着差异表达可能会指导相关分子网络的变化。此外，上调的脑 5-HT 可作为斑马鱼持续性 AMI 发病机制的中枢调节剂。考虑到天然水中的 AMI 残留量可能暂时超过微克/升，因此不应忽视对硬骨鱼的相应持续性不利影响。它们的显着差异表达可能会指导相关分子网络的变化。此外，上调的脑 5-HT 可作为斑马鱼持续性 AMI 发病机制的中枢调节剂。考虑到天然水中的 AMI 残留量可能暂时超过微克/升，因此不应忽视对硬骨鱼的相应持续性不利影响。