Abstract
The zebrafish (Danio rerio) is a model animal that is being increasingly used in neuroscience research. A decade ago, the first study on unpredictable chronic stress (UCS) in zebrafish was published, inspired by protocols established for rodents in the early 1980s. Since then, several studies have been published by different groups, in some cases with conflicting results. Here we conducted a systematic review to identify studies evaluating the effects of UCS in zebrafish and meta-analytically synthetized the data of neurobehavioral outcomes and relevant biomarkers. Literature searches were performed in three databases (PubMed, Scopus and Web of Science) with a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk-of-bias assessment. Outcomes of included studies (n = 38) were grouped into anxiety/fear-related behavior, locomotor function, social behavior or cortisol level domains. UCS increased anxiety/fear-related behavior and cortisol levels while decreasing locomotor function, but a significant summary effect was not observed for social behavior. Despite including a substantial number of studies, the high heterogeneity and the methodological and reporting problems evidenced in the risk-of-bias analysis made it difficult to assess the internal validity of most studies and the overall validity of the model. Our review thus evidences the need to conduct well-designed experiments to better evaluate the effects of UCS on diverse behavioral patterns displayed by zebrafish.
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Acknowledgements
The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, proc. 303343/2020-6), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES), and Pró-Reitoria de Pesquisa (PROPESQ) at Universidade Federal do Rio Grande do Sul (UFRGS) for funding and support.
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M.G.-L., A.P. and A.P.H. conceived and designed the project. M.G.-L. and A.P.H. curated acquired data and administrated the project. A.P.H. supervised the project. M.G.-L., A.C.P. and A.P.H. collaborated on the formal analysis and data visualization. M.G.-L., L.M.B., R.B., A.P. and A.P.H. contributed to the investigation and methodology. M.G.-L. drafted the article. L.M.B., R.B., A.C.P., A.P. and A.P.H. provided critical revisions of the article.
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Gallas-Lopes, M., Bastos, L.M., Benvenutti, R. et al. Systematic review and meta-analysis of 10 years of unpredictable chronic stress in zebrafish. Lab Anim 52, 229–246 (2023). https://doi.org/10.1038/s41684-023-01239-5
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DOI: https://doi.org/10.1038/s41684-023-01239-5