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The Three-Chamber Choice Behavioral Task using Zebrafish as a Model System
Published on: April 14, 2021
Assessing the Value of the Zebrafish Conditioned Place Preference Model for Predicting Human Abuse Potential
A J Brock1, S M G Goody1, A N Mead1
1School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom (A.J.B., A.S., C.H.B.); Global Safety Pharmacology, Drug Safety Research and Development, Pfizer Worldwide Research and Development, Groton, Connecticut (S.M.G.G., A.N.M.); and School of Health Sciences and Social Work, University of Portsmouth, Portsmouth, United Kingdom (M.O.P.).
The zebrafish conditioned place preference (CPP) model does not reliably predict human drug abuse potential or scheduling. Traditional preclinical models in rats and non-human primates (NHPs) show greater predictive value for drug abuse liability.
Area of Science:
- Pharmacology
- Neuroscience
- Drug Abuse Research
Background:
- Regulatory agencies require abuse potential testing for centrally active drugs.
- Standard preclinical models include rats and non-human primates (NHPs).
- The zebrafish conditioned place preference (CPP) model is a potential alternative for abuse potential assessment.
Purpose of the Study:
- To evaluate the predictive accuracy of the zebrafish CPP model for human drug abuse outcomes.
- To compare the efficacy of zebrafish CPP with rat and NHP models in predicting abuse potential.
- To assess the utility of zebrafish CPP in predicting drug scheduling by regulatory agencies.
Main Methods:
- Twenty-seven diverse compounds were tested using zebrafish CPP.
- Compounds were classified as positive or negative predictors of abuse potential.
- Standard binary classification tests were used to analyze predictive values.
- Results were compared against human subjective effects studies (+HSE) and drug scheduling outcomes.
- Zebrafish data were benchmarked against rat and NHP self-administration and CPP data.
Main Results:
- Zebrafish CPP showed no significant difference from chance in predicting +HSE or drug scheduling.
- While specificity improved for +HSE, low sensitivity limited predictive value.
- Zebrafish assessments provided no added value for predicting drug scheduling.
- Rat and NHP models demonstrated significantly higher concordance, sensitivity, and positive predictive values.
- Potential predictive value for specific drug classes (e.g., opioids, psychostimulants) in zebrafish CPP was noted but overall limited.
Conclusions:
- The current zebrafish CPP methodology does not add significant value to preclinical abuse potential assessment.
- Rat and NHP models remain more reliable for predicting human drug abuse outcomes and regulatory scheduling.
- Further research may refine zebrafish models for specific drug classes, but current utility is limited.
