title: Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline.
abstract: Several model organisms have been employed to study the impacts of stress on biological systems. Different models of unpredictable chronic stress (UCS) have been established in rodents; however, these protocols are expensive, long-lasting, and require a large physical structure. Our group has recently reported an UCS protocol in zebrafish with several advantages compared to rodent models. We observed that UCS induced behavioral, biochemical, and molecular changes similar to those observed in depressed patients, supporting the translational relevance of the protocol.
  
  
  
  Considering that a pharmacological assessment is lacking in this zebrafish model, our aim was to evaluate the effects of anxiolytic (bromazepam) and antidepressant drugs (fluoxetine and nortriptyline) on behavioral (novel tank test), biochemical (whole-body cortisol), and molecular parameters (cox-2, tnf-α, il-6, and il-10 gene expression) in zebrafish subjected to UCS.
  
  
  
  We replicated previous data showing that UCS induces behavioral and neuroendocrine alterations in zebrafish, and we show for the first time that anxiolytic and antidepressant drugs are able to prevent such effects. Furthermore, we extended the molecular characterization of the model, revealing that UCS increases expression of the pro-inflammatory markers cox-2 and il-6, which was also prevented by the drugs tested.
  
  
  
  This study reinforces the use of zebrafish as a model organism to study the behavioral and physiological effects of stress. The UCS protocol may also serve as a screening tool for evaluating new drugs that can be used to treat psychiatric disorders with stress-related etiologies.
authors: Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Av. Senador Attílio Fontana, 591E, Chapecó, Santa Catarina, 89809-000, Brazil.
authors: Matheus
authors: M
authors: Marcon
authors: Grupo de Estudos Biológicos e Clínicos em Patologias Humanas, Universidade Federal da Fronteira Sul, Campus Chapecó, SC 484 km 02, Chapecó, Santa Catarina, 89815-899, Brazil.
authors: Ana P
authors: AP
authors: Herrmann
authors: Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Av. Senador Attílio Fontana, 591E, Chapecó, Santa Catarina, 89809-000, Brazil.
authors: Ricieri
authors: R
authors: Mocelin
authors: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors: Cassiano L
authors: CL
authors: Rambo
authors: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Campus Universitário, Camobi, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors: Gessi
authors: G
authors: Koakoski
authors: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Campus Universitário, Camobi, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors: Murilo S
authors: MS
authors: Abreu
authors: Laboratório de Fisiologia da Reprodução Animal, Universidade Federal de Santa Catarina, Rodovia Ulisses Gaboardi, km 3, Centro de Curitibanos, Curitibanos, Santa Catarina, 89520-000, Brazil.
authors: Greicy M M
authors: GM
authors: Conterato
authors: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors: Luiza W
authors: LW
authors: Kist
authors: Programa de Pós-Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6681, Porto Alegre, RS, 90619-900, Brazil.
authors: Maurício R
authors: MR
authors: Bogo
authors: Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Av. Senador Attílio Fontana, 591E, Chapecó, Santa Catarina, 89809-000, Brazil.
authors: Leila
authors: L
authors: Zanatta
authors: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Campus Universitário, Camobi, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.|Programa de Pós-Graduação em Bioexperimentação, Universidade de Passo Fundo, BR 285, Passo Fundo, Rio Grande do Sul, 99052-900, Brazil.
authors: Leonardo J G
authors: LJ
authors: Barcellos
authors: Laboratório de Psicofarmacologia e Comportamento, Programa de Pós-Graduação em Farmacologia e Terapêutica, ICBS, Universidade Federal do Rio Grande do Sul, Av. Sarmento Leite 500/305, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. angelopiato@ufrgs.br.|Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA. angelopiato@ufrgs.br.
authors: Angelo L
authors: AL
authors: Piato
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001960:Bromazepam / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism; D009661:Nortriptyline / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D016753:Interleukin-10; D009661:Nortriptyline; D051546:Cyclooxygenase 2; D006854:Hydrocortisone; D001960:Bromazepam
keywords: Antidepressants; Anxiolytics; Cortisol; Cytokines; Unpredictable chronic stress