McDonald M Danielle
Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL 33149, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2017 Jul;197:19-31. doi: 10.1016/j.cbpc.2017.03.007. Epub 2017 Mar 10.
Pharmaceuticals and personal care products (PPCPs) are found in measureable quantities within the aquatic environment. Selective serotonin reuptake inhibitor (SSRI) antidepressants are one class of pharmaceutical compound that has received a lot of attention. Consistent with most PPCPs, the pharmacokinetics and physiological impacts of SSRI treatment have been well-studied in small mammals and humans and this, combined with the evolutionary conservation of the serotonergic system across vertebrates, allows for the read-across of known SSRI effects in mammals to potential SSRI impacts on aquatic organisms. Using an Adverse Outcome Pathway (AOP) framework, this review examines the similarities and differences between the mammalian and teleost fish SSRI target, the serotonin transporter (SERT; SLC6A4), and the downstream impacts of elevated extracellular serotonin (5-HT; 5-hydroxytryptamine), the consequence of SERT inhibition, on organ systems and physiological processes within teleost fish. This review also intends to reveal potentially understudied endpoints for SSRI toxicity based on what is known to be controlled by 5-HT in fish.
在水生环境中可检测到药物和个人护理产品（PPCPs）。选择性5-羟色胺再摄取抑制剂（SSRI）类抗抑郁药是一类备受关注的药物化合物。与大多数PPCPs一样，SSRI治疗的药代动力学和生理影响已在小型哺乳动物和人类中得到充分研究，再加上脊椎动物血清素能系统的进化保守性，使得已知的哺乳动物中SSRI的影响能够类推到其对水生生物的潜在影响。本综述使用不良结局途径（AOP）框架，研究了哺乳动物和硬骨鱼的SSRI靶点——血清素转运体（SERT；SLC6A4）之间的异同，以及细胞外血清素（5-HT；5-羟色胺）升高的下游影响，即SERT抑制对硬骨鱼器官系统和生理过程的影响。本综述还旨在根据已知的鱼类中受5-HT控制的情况，揭示SSRI毒性可能未被充分研究的终点。
