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首页> 外文期刊>Environmental Science & Technology >Human Therapeutic Plasma Levels of the Selective Serotonin Reuptake Inhibitor (SSRI) Sertraline Decrease Serotonin Reuptake Transporter Binding and Shelter-Seeking Behavior in Adult Male Fathead Minnows
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Human Therapeutic Plasma Levels of the Selective Serotonin Reuptake Inhibitor (SSRI) Sertraline Decrease Serotonin Reuptake Transporter Binding and Shelter-Seeking Behavior in Adult Male Fathead Minnows

机译:选择性5-羟色胺再摄取抑制剂(SSRI)舍曲林的人体治疗血浆水平降低成年雄性黑头黑猩猩中5-羟色胺再摄取转运蛋白的结合和庇护行为

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摘要

Selective serotonin reuptake inhibitors (SSRIs) represent a class of pharmaceuticals previously reported in aquatic ecosystems. SSRIs are designed to treat depression and other disorders in humans, but are recognized to elicit a variety of effects on aquatic organisms, ranging from neuroendocrine disruption to behavioral perturbations. However, an understanding of the relationships among mechanistic responses associated with SSRI targets and ecologically important behavioral responses of fish remains elusive. Herein, linking Adverse Outcomes Pathways (AOP) models with internal dosimetry represent potential approaches for developing an understanding of pharmaceutical risks to aquatic life. We selected sertraline as a model SSRI for a 28-d study with adult male fathead minnows. Binding activity of the serotonin reuptake transporter (SERT), previously demonstrated in mammals and fish models to respond to sertraline exposure, was selected as an endpoint associated with therapeutic activity. Shelter-seeking behavior was monitored using digital tracking software to diagNO_xe behavioral abnormalities. Fish plasma levels of sertraline exceeding human therapeutic doses were accurately modeled from external exposure concentrations when pH influences on ionization and log D were considered. We observed statistically significant decreases in binding at the therapeutic target (SERT) and shelter-seeking behavior when fish plasma levels exceeded human therapeutic thresholds. Such observations highlights the strengths of coupling physiologically based pharmacokinetic modeling and AOP approaches and suggest that internal dosimetry should be monitored to advance an understanding of the ecological consequences of SSRI exposure to aquatic vertebrates.
机译:选择性5-羟色胺再摄取抑制剂(SSRIs)代表先前在水生生态系统中报道的一类药物。 SSRI被设计用于治疗人类的抑郁症和其他疾病,但是公认可以引起对水生生物的多种影响,从神经内分泌破坏到行为扰动。但是,对与SSRI目标相关的机械反应与鱼类的重要生态行为反应之间的关系的了解仍然难以捉摸。在本文中,将不良结果途径(AOP)模型与内部剂量测定法联系起来代表了潜在的方法,可用于加深对药物对水生生物风险的了解。我们选择了舍曲林作为SSRI模型,进行了成年雄性黑头min鱼的28天研究。选择5-羟色胺再摄取转运蛋白(SERT)的结合活性作为与治疗活性相关的终点,该结合活性先前已在哺乳动物和鱼类模型中证明对舍曲林的暴露有反应。使用数字跟踪软件监视避难行为,以诊断行为异常。当考虑到pH对电离和log D的影响时,可以根据外部暴露浓度精确模拟出超过人治疗剂量的鱼血舍曲林水平。当鱼血浆水平超过人类治疗阈值时,我们观察到在治疗目标(SERT)处的结合和寻求避难所的行为在统计学上显着降低。这些观察结果突出了基于生理学的药代动力学建模和AOP方法耦合的优势,并建议应监测内部剂量,以加深对SSRI暴露于水生脊椎动物的生态后果的了解。

著录项

  • 来源
    《Environmental Science & Technology》 |2012年第4期|p.2427-2435|共9页
  • 作者单位

    The Institute of Ecological, Earth, and Environmental Sciences, Baylor University, Waco, Texas 76798, United States,Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798,United States,U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecological Division,Duluth, MN 55804;

    University of Texas Health Science Center at San Antonio, Department of Physiology, MC 7756, 7703 Floyd Curl Drive, San Antonio, Texas 78229, United States;

    Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States,Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798,United States;

    Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States,Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798,United States;

    Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States,Department of Psychology and Neuroscience, Baylor University, Waco, Texas 76798, United States;

    Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798,United States;

    The Institute of Ecological, Earth, and Environmental Sciences, Baylor University, Waco, Texas 76798, United States,Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States,Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798,United States;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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