Centre for Advanced Research in Environmental Genomics and Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
J Toxicol Environ Health B Crit Rev. 2011;14(5-7):387-412. doi: 10.1080/10937404.2011.578559.
Pharmaceuticals are increasingly detected in a variety of aquatic systems. One of the most prevalent environmental pharmaceuticals in North America and Europe is the antidepressant fluoxetine, a selective serotonin reuptake inhibitor (SSRI) and the active ingredient of Prozac. Usually detected in the range below 1 μg/L, fluoxetine and its active metabolite norfluoxetine are found to bioaccumulate in wild-caught fish, particularly in the brain. This has raised concerns over potential disruptive effects of neuroendocrine function in teleost fish, because of the known role of serotonin (5-HT) in the modulation of diverse physiological processes such as reproduction, food intake and growth, stress and multiple behaviors. This review describes the evolutionary conservation of the 5-HT transporter (the therapeutic target of SSRIs) and reviews the disruptive effects of fluoxetine on several physiological endpoints, including involvement of neuroendocrine mechanisms. Studies on the goldfish, Carassius auratus, whose neuroendocrine regulation of reproduction and food intake are well characterized, are described and represent a reliable model to study neuroendocrine disruption. In addition, fish studies investigating the effects of fluoxetine, not only on reproduction and food intake, but also on stress and behavior, are discussed to complement the emerging picture of neuroendocrine disruption of physiological systems in fish exposed to fluoxetine. Environmental relevance and key lessons learned from the effects of the antidepressant fluoxetine on fish are highlighted and may be helpful in designing targeted approaches for future risk assessments of pharmaceuticals disrupting the neuroendocrine system in general.
药品在各种水生系统中越来越多地被检出。在北美和欧洲，最普遍的环境药品之一是抗抑郁药氟西汀，它是一种选择性 5-羟色胺再摄取抑制剂（SSRI），也是百忧解（Prozac）的有效成分。氟西汀及其活性代谢物去甲氟西汀通常在 1μg/L 以下被检出，在野生捕获的鱼类中被发现具有生物蓄积性，尤其是在大脑中。这引起了人们对 5-羟色胺（5-HT）在调节鱼类多种生理过程（如繁殖、摄食和生长、应激和多种行为）中的神经内分泌功能潜在干扰作用的关注，因为 5-HT 已知在这些过程中发挥作用。本文描述了 5-羟色胺转运体（SSRIs 的治疗靶点）的进化保守性，并综述了氟西汀对几种生理终点的干扰作用，包括涉及神经内分泌机制的作用。本文描述了金鱼（Carassius auratus）的研究，金鱼的繁殖和摄食的神经内分泌调节已得到很好的描述，它是研究神经内分泌干扰的可靠模型。此外，还讨论了鱼类研究中氟西汀对繁殖和摄食、应激和行为的影响，以补充氟西汀暴露对鱼类生理系统的神经内分泌干扰的新图景。本文强调了从氟西汀对鱼类的影响中获得的环境相关性和关键教训，这可能有助于设计针对一般扰乱神经内分泌系统的药品的未来风险评估的靶向方法。
