title: Aquatic toxicology of fluoxetine: understanding the knowns and the unknowns.
abstract: Fluoxetine is one of the most prescribed psychotropic medications, and is an agent of increasing interest for environmental toxicology. Fish and other aquatic organisms are excellent models to study neuroactive small molecules like fluoxetine. However, prone to variance due to experimental factors, data obtained in these models need to be interpreted with caution, using proper experimental protocols, study designs, validated endpoints as well as well-established models and tests. Choosing the treatment protocol and dose range for fluoxetine and other serotonergic drugs is critical for obtaining valid test results and correct data interpretation. Here we discuss the value of aquatic models to study fluoxetine effects, based on prior high-quality research, and outline the directions of future translational studies in the field. We review fluoxetine-evoked phenotypes in acute vs. chronic protocols, discussing them in the contact of complex role of serotonin in behavioral regulation. We conclude that zebrafish and other aquatic models represent a useful in-vivo tool for fluoxetine pharmacology and (eco)toxicology research.
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA.
authors.forename: Adam Michael
authors.initials: AM
authors.lastname: Stewart
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA; St. George's University School of Medicine, Grenada, WI, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Grossman
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA; Department of Biomedical Engineering, University of Virginia, 415 Lane Road, Charlottesville, VA 22908, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA; Center for Biological and Health Sciences, State University of Para, Maraba, Para, Brazil.
authors.forename: Caio
authors.initials: C
authors.lastname: Maximino
authors.affiliation: The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA; Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, 1000 Roraima Ave, Santa Maria, Brazil.
authors.forename: Denis Broock
authors.initials: DB
authors.lastname: Rosemberg
authors.affiliation: The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA; Department of Psychology, University of Southern Mississippi, 118 College Drive, Hattiesburg, MS 39406, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Echevarria
authors.affiliation: ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA; Research Institute of Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong 524088, China. Electronic address: avkalueff@gmail.com.
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
mesh_terms: D000818:Animals; D059001:Aquatic Organisms / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D054750:Ecotoxicology / Q000592:standards*; D005473:Fluoxetine / Q000633:toxicity*; D023421:Models, Animal; D012701:Serotonin / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish
chemical_list: D014874:Water Pollutants, Chemical; D005473:Fluoxetine; D012701:Serotonin
keywords: Antidepressants; Aquatic model; Ecotoxicology; Fluoxetine; Neuroscience; Zebrafish