Growth and development of tadpoles (Xenopus laevis) exposed to selective serotonin reuptake inhibitors, fluoxetine and sertraline, throughout metamorphosis

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed drugs that are present in sewage effluents and surface waters. The objective of the present study was to determine whether low environmentally relevant concentrations of the SSRIs fluoxetine and sertraline could impair growth and development in tadpoles of the African clawed frog (Xenopus laevis) and to evaluate if such effects may be caused by a disruption of the neuroendocrine system. Tadpoles were exposed to SSRIs at concentrations of 0.1, 1, and 10 microg/L for 70 d throughout metamorphosis. No effects on deformities were observed. Tadpoles exposed to fluoxetine (10 microg/L) and sertraline (0.1, 1, and 10 microg/L) exhibited reduced growth at metamorphosis. Tadpoles exposed to sertraline (0.1 and 1 microg/L) exhibited an acceleration of development as indicated by an increase in the time to tail resorption. The effects of SSRIs on growth and development in tadpoles were likely driven by reduced food intake. Reduced feeding rates were observed in SSRI-exposed tadpoles, and nutritional status can influence growth and development in amphibians via effects on the neuroendocrine system. Only sertraline was capable of causing developmental toxicity in tadpoles at environmentally relevant concentrations. These data warrant additional research to characterize the risks to human health and wildlife from pharmaceutical exposures.

[1]  Alejandro J. Ramirez,et al.  Determination of select antidepressants in fish from an effluent‐dominated stream , 2005, Environmental toxicology and chemistry.

[2]  Daniel J. Flannery,et al.  Outcomes in young adulthood for very-low-birth-weight infants. , 2002, The New England journal of medicine.

[3]  T. Ternes,et al.  Pharmaceuticals and personal care products in the environment: agents of subtle change? , 1999, Environmental health perspectives.

[4]  S. Hernández-Díaz,et al.  First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. , 2007, The New England journal of medicine.

[5]  C. Olsson,et al.  The control of gut motility. , 2001, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[6]  M. Slattery,et al.  Reproductive Assessment of Japanese Medaka (Oryzias latipes) Following a Four-Week Fluoxetine (SSRI) Exposure , 2004, Archives of environmental contamination and toxicology.

[7]  K. Armbrust,et al.  Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia , 2004, Environmental toxicology and chemistry.

[8]  L. Zhang,et al.  Hypothalamic dopamine and serotonin in the regulation of food intake. , 2000, Nutrition.

[9]  D. Wake,et al.  Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Vorhees,et al.  A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. , 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[11]  A. Gitelman,et al.  Carryover aquatic effects on survival of metamorphic frogs during pond emigration. , 2006, Ecological applications : a publication of the Ecological Society of America.

[12]  E. Michael Thurman,et al.  Response to Comment on “Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999−2000: A National Reconnaissance” , 2002 .

[13]  B. Levy,et al.  Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. , 2004, The American journal of psychiatry.

[14]  J. Faber,et al.  Normal table of Xenopus laevis (Daudin). A systematical and chronological survey of the development from the fertilized egg till the end of metamorphosis. , 1956 .

[15]  Paige L. Williams,et al.  NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of fluoxetine. , 2004, Birth defects research. Part B, Developmental and reproductive toxicology.

[16]  J. Littleton Receptor regulation as a unitary mechanism for drug tolerance and physical dependence--not quite as simple as it seemed! , 2001, Addiction.

[17]  K. Crofton,et al.  Screening methods for thyroid hormone disruptors. , 1999, Environmental health perspectives.

[18]  D. Kelley,et al.  Prolactin opens the sensitive period for androgen regulation of a larynx-specific myosin heavy chain gene. , 1999, Journal of neurobiology.

[19]  D. Marino,et al.  Comparative susceptibility to atrazine of three developmental stages of Rhinella arenarum and influence on metamorphosis: non-monotonous acceleration of the time to climax and delayed tail resorption. , 2009, Aquatic toxicology.

[20]  Jan M Friedman,et al.  Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. , 2007, The New England journal of medicine.

[21]  R. Relyea Getting out alive: how predators affect the decision to metamorphose , 2007, Oecologia.

[22]  K. Barros,et al.  Sertraline delays the somatic growth and reflex ontogeny in neonate rats , 2006, Physiology & Behavior.

[23]  G. Pinna,et al.  Printed in U.S.A. Copyright © 2000 by The Endocrine Society Effects of Pharmacological and Nonpharmacological Treatments on Thyroid Hormone Metabolism and Concentrations in Rat Brain* , 1999 .

[24]  D. E. Scott,et al.  Time and size at metamorphosis related to adult fitness in Ambystoma talpoideum , 1988 .

[25]  R. Brain,et al.  Exposure assessment and microcosm fate of selected selective serotonin reuptake inhibitors. , 2005, Regulatory toxicology and pharmacology : RTP.

[26]  Edward J. Calabrese,et al.  Hormesis: Why it is important to toxicology and toxicologists , 2008 .

[27]  Thomas Braunbeck,et al.  Description and initial evaluation of a Xenopus metamorphosis assay for detection of thyroid system‐disrupting activities of environmental compounds , 2005, Environmental toxicology and chemistry.

[28]  R. Denver PROXIMATE MECHANISMS OF PHENOTYPIC PLASTICITY IN AMPHIBIAN METAMORPHOSIS , 1997 .

[29]  Yunbo Shi Amphibian Metamorphosis: From Morphology to Molecular Biology , 1999 .

[30]  R. Blakely,et al.  Serotonin Transporter Function Is an Early Step in Left-Right Patterning in Chick and Frog Embryos , 2005, Developmental Neuroscience.

[31]  J. Faber,et al.  The role of thyroid hormones in depression. , 1998, European journal of endocrinology.

[32]  C. Hertzman,et al.  Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. , 2006, Archives of general psychiatry.

[33]  C. Lowry,et al.  Regulation of behavioral responses by corticotropin-releasing factor. , 2006, General and comparative endocrinology.

[34]  A. Nicieza Interacting effects of predation risk and food availability on larval anuran behaviour and development , 2000, Oecologia.

[35]  R. Denver,et al.  Ontogeny of corticotropin-releasing factor effects on locomotion and foraging in the Western spadefoot toad (Spea hammondii) , 2004, Hormones and Behavior.

[36]  John Struger,et al.  Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada , 2003, Environmental toxicology and chemistry.

[37]  E. Thurman,et al.  Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. , 2002 .