title: Pharmaceuticals as neuroendocrine disruptors: lessons learned from fish on Prozac.
abstract: 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.
authors.affiliation: Centre for Advanced Research in Environmental Genomics and Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Mennigen
authors.forename: Pamela
authors.initials: P
authors.lastname: Stroud
authors.forename: Jake M
authors.initials: JM
authors.lastname: Zamora
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005399:Fishes; D005473:Fluoxetine / Q000633:toxicity*; D006054:Goldfish; D008954:Models, Biological; D009490:Neurosecretory Systems / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D052244:Endocrine Disruptors; D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014874:Water Pollutants, Chemical