4.1 Article

Zebrafish (Danio rerio) larvae show behavioral and embryonic development defects when exposed to opioids at embryo stage

Journal

NEUROTOXICOLOGY AND TERATOLOGY
Volume 85, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2021.106964

Keywords

Zebrafish embryotoxicity; Swimming activity; Locomotor behavior; Morphine; Codeine; Eye defect

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - CAPES [88887.364263/2019-00]
  2. NIH/NIAAA [1 R21 AA026711]
  3. UFRPE

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This study evaluated the effect of early embryonic opioid exposure on zebrafish development, with results showing that high concentrations and longer exposure times of opioids can lead to hypoactive behavior in animals during dark periods. Further research is needed to understand the neural defects underlying these behavior changes.
Opioid abuse continues to plague society, and in recent years, there has been an epidemic, leading to increased addiction and death. It is poorly understood how prenatal opioid use affects the lives of children. The aim of this work was to evaluate the effect of early embryonic codeine or morphine exposure in zebrafish (Danio rerio), examining gastrulation progression (epiboly), teratogenic effects, mortality and locomotor behavior response to light/dark cycles. Zebrafish embryos were exposed to codeine or morphine (designated C or M) at 1, 5 or 10 mg/ L (designated 01, 05 or 10, respectively) from 3 to 24 h postfertilization (hpf) or from 3 to 48 hpf (designated-24 or -48 for 1 or 2 days of exposure, respectively). The C10-24, C01-48, C05-48 and C10-48 groups showed significantly smaller eyes than control larvae at 7 days postfertilization (dpf). Locomotor behavior of control larvae in light/dark cycles showed greater swimming time and distance in dark cycles. Two-day codeine exposure produced strong effects, showing no significant response due to light/dark cycles in distance moved. Morphine exposed groups showed similar effects as observed in 2-day codeine exposed groups, showing less large movement activity and also no significant difference between inactive duration in response to light/dark cycles. In conclusion, we observed low teratogenic effects and mortality effects. Animals exposed to high levels and higher exposure times of opioids were hypoactive, relative to controls, in the dark period. Future studies will be needed to understand the neural defects producing behavior changes.

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