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Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays
by
, , , , , , , and
Alexey Sarapultsev
1,2,*,
Maria Komelkova
2,
Oleg Lookin
3,
Sergey Khatsko
4,
Alexander Zhdanov
4,
Stanislav Fedorov
2,
Evgenii Gusev
1
,
Alexander Trofimov
5
,
Tursonjan Tokay
5 and
Desheng Hu
6,7 1
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia
2
Russian–Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia
3
National Scientific Medical Center, Astana 010009, Kazakhstan
4
Anatomical and Physiological Experimental Laboratory, Department of Experimental Biology and Biotechnology, Institute of Natural Sciences and Mathematics, 48 Kuybysheva Str., 620026 Ekaterinburg, Russia
5
Biology Department, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbai Batyr Ave., Astana 010000, Kazakhstan
6
Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
7
Hubei Key Laboratory of Biological Targeted Therapy, China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
*
Author to whom correspondence should be addressed.
Biology 2025, 14(8), 939; https://doi.org/10.3390/biology14080939
Submission received: 18 June 2025
/
Revised: 18 July 2025
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Accepted: 24 July 2025
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Published: 25 July 2025
(This article belongs to the Special Issue Social Behavior in Zebrafish)
Simple Summary
Post-traumatic stress disorder is a serious mental health condition that can develop after experiencing or witnessing traumatic events. To better understand how this condition affects the brain and behavior, scientists use animal models that can mimic aspects of trauma and stress. In this study, we review the use of zebrafish—a small tropical freshwater fish—as a model for studying post-traumatic stress. Zebrafish are increasingly used because they share many important biological features with humans, respond to stress in similar ways, and can be studied at all stages of development. We describe how different stress models, such as exposure to predators, social isolation, or unpredictable stressful events, affect zebrafish behavior and biology. Importantly, we also highlight the fish’s ability to learn from experience, remember traumatic events, and show long-term changes in behavior—similar to symptoms seen in people with post-traumatic stress. Our analysis suggests that zebrafish are a valuable and affordable research tool for discovering how stress-related disorders develop and how they might be treated. Understanding stress responses in zebrafish can help researchers develop better ways to prevent and manage trauma-related mental health conditions in humans.
Abstract
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system.
