PUBLICATION

Chronic exposure to oxazepam pollution produces tolerance to anxiolytic effects in zebrafish (Danio rerio)

Authors
Vossen, L.E., Cerveny, D., Österkrans, M., Thörnqvist, P.O., Jutfelt, F., Fick, J., Brodin, T., Winberg, S.
ID
ZDB-PUB-200115-10
Date
2020
Source
Environmental science & technology   54(3): 1760-1769 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Anti-Anxiety Agents*
  • Environmental Pollution
  • Female
  • Male
  • Oxazepam
  • Water Pollutants, Chemical*
  • Zebrafish
PubMed
31934760 Full text @ Env. Sci. Tech.
Abstract
Environmental concentrations of the anxiolytic drug oxazepam have been found to disrupt anti-predator behaviors of wild fish. Most experiments exposed fish for a week, while evidence from mammals suggests that chronic exposure to therapeutic concentrations of benzodiazepines (such as oxazepam) results in the development of tolerance to the anxiolytic effects. If tolerance can also develop in response to the low concentrations found in the aquatic environment, it could mitigate the negative effects of oxazepam pollution. In the current study, we exposed wild-caught zebrafish to oxazepam (~7 μg L-1) for 7 or 28 days and evaluated behavioral and physiological parameters at both time points. Females showed reduced diving responses to conspecific alarm pheromone after 7 days, but not after 28 days, indicating that they had developed tolerance to the anxiolytic effects of the drug. Zebrafish males were not affected by this oxazepam concentration, in line with earlier results. Serotonin turnover (ratio 5-HIAA/ 5-HT) was reduced in exposed females and males after 28 days, indicating that brain neurochemistry had not normalized. Post-confinement cortisol concentrations and gene expression of corticotropin releasing hormone (CRH) were not affected by oxazepam. We did not find evidence that chronically exposed fish had altered relative expression of GABAA receptor subunits, suggesting that some other still unknown mechanism caused the developed tolerance.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping