Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays
Sarapultsev A. Komelkova M. Lookin O. Khatsko S. Zhdanov A. Fedorov S. Gusev E. Trofimov A. Tokay T. Hu D.
August 2025Multidisciplinary Digital Publishing Institute (MDPI)
Biology
2025#14Issue 8
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.
behavioral changes , experimental models , molecular mechanisms , post-traumatic stress disorder , stress-related neurophysiological alterations , zebrafish (Danio rerio)
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Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, Ekaterinburg, 620049, Russian Federation
Russian–Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, Chelyabinsk, 454080, Russian Federation
National Scientific Medical Center, Astana, 010009, Kazakhstan
Anatomical and Physiological Experimental Laboratory, Department of Experimental Biology and Biotechnology, Institute of Natural Sciences and Mathematics, 48 Kuybysheva Str., Ekaterinburg, 620026, Russian Federation
Biology Department, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbai Batyr Ave., Astana, 010000, Kazakhstan
Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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
Institute of Immunology and Physiology
Russian–Chinese Education and Research Center of System Pathology
National Scientific Medical Center
Anatomical and Physiological Experimental Laboratory
Biology Department
Department of Integrated Traditional Chinese and Western Medicine
Hubei Key Laboratory of Biological Targeted Therapy
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