抗抑郁药(ADDs)是全球使用最广泛的药物之一。它们在特别低的治疗浓度下调节单胺神经传递,这是人类和包括无脊椎动物在内的动物物种中进化最保守的途径之一。由于在水生环境中广泛检测到低浓度的ADD(ng/L至低µg/L),它们在水生物种中发挥药物靶标介导作用的潜力引起了人们的严重关注。阿米替林(AMI)是最广泛使用的三环ADD,而单胺,ADDs的目标,是多个关键生理过程的主要生物调节剂,包括喂养,软体动物的繁殖和行为。然而,AMI对摄食的影响,尽管软体动物的生态重要性,但它们的繁殖和交配行为是未知的,多样性和报告的ADDs敏感性。为了解决这个知识差距,我们调查了环境相关浓度的AMI(0,10,100,500和1000ng/L)对饲料的影响,繁殖和关键的运动行为,包括交配,在淡水腹足动物中,在28天的时间内的光滑生物。为了进一步深入了解软体动物对ADD的敏感性,使用新型提取方法确定AMI浓度(暴露水和血淋巴)。鱼血浆模型(FPM)一种对药物进行优先级评估的关键工具,有可能在鱼类中引起药物靶标介导的影响,然后首次评估了其对软体动物的适用性。在AMI的血淋巴水平特别低的情况下,观察到食物摄入(1000ng/L)和生殖输出(500和1000ng/L)的破坏,而运动行为不受影响。重要的是,使用FPM预测的AMI血淋巴水平与测量水平非常吻合。研究结果表明,AMI的血淋巴水平可能是淡水腹足类野生种群摄食和生殖破坏的有用指标,并确认FPM对软体动物的适用性,以进行比较药物危害识别。
Antidepressant drugs (ADDs) are one of the most extensively used pharmaceuticals globally. They act at particularly low therapeutic concentrations to modulate monoamine neurotransmission, which is one of the most evolutionary conserved pathways in both humans and animal species including invertebrates. As ADDs are widely detected in the aquatic environment at low concentrations (ng/L to low µg/L), their potential to exert drug-target mediated effects in aquatic species has raised serious concerns. Amitriptyline (AMI) is the most widely used tricyclic ADD, while monoamines, the target of ADDs, are major bioregulators of multiple key physiological processes including feeding, reproduction and behaviour in molluscs. However, the effects of AMI on feeding, reproduction and mating behaviour are unknown in molluscs despite their ecological importance, diversity and reported sensitivity to ADDs. To address this knowledge gap, we investigated the effects of environmentally relevant concentrations of AMI (0, 10, 100, 500 and 1000 ng/L) on feeding, reproduction and key locomotor behaviours, including mating, in the freshwater gastropod, Biomphalaria glabrata over a period of 28 days. To further provide insight into the sensitivity of molluscs to ADDs, AMI concentrations (exposure water and hemolymph) were determined using a novel extraction method. The Fish Plasma Model (FPM), a critical tool for prioritization assessment of pharmaceuticals with potential to cause drug target-mediated effects in fish, was then evaluated for its applicability to molluscs for the first time. Disruption of food intake (1000 ng/L) and reproductive output (500 and 1000 ng/L) were observed at particularly low hemolymph levels of AMI, whereas locomotor behaviours were unaffected. Importantly, the predicted hemolymph levels of AMI using the FPM agreed closely with the measured levels. The findings suggest that hemolymph levels of AMI may be a useful indicator of feeding and reproductive disruptions in wild population of freshwater gastropods, and confirm the applicability of the FPM to molluscs for comparative pharmaceutical hazard identification.