PUBLICATION

Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline

Authors
Marcon, M., Herrmann, A.P., Mocelin, R., Rambo, C.L., Koakoski, G., Abreu, M.S., Conterato, G.M., Kist, L.W., Bogo, M.R., Zanatta, L., Barcellos, L.J., Piato, A.L.
ID
ZDB-PUB-160827-5
Date
2016
Source
Psychopharmacology   233(21-22): 3815-3824 (Journal)
Registered Authors
Keywords
Antidepressants, Anxiolytics, Cortisol, Cytokines, Unpredictable chronic stress
MeSH Terms
  • Animals
  • Anti-Anxiety Agents/pharmacology*
  • Antidepressive Agents/pharmacology*
  • Behavior, Animal/drug effects*
  • Bromazepam/pharmacology*
  • Cyclooxygenase 2/drug effects
  • Cyclooxygenase 2/metabolism
  • Disease Models, Animal
  • Female
  • Fluoxetine/pharmacology*
  • Hydrocortisone/metabolism
  • Interleukin-10/metabolism
  • Interleukin-6/metabolism
  • Male
  • Neurosecretory Systems/drug effects
  • Neurosecretory Systems/metabolism
  • Nortriptyline/pharmacology*
  • Stress, Psychological/metabolism*
  • Tumor Necrosis Factor-alpha/drug effects
  • Tumor Necrosis Factor-alpha/metabolism
  • Zebrafish
PubMed
27562666 Full text @ Psychpharma
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping