Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests

Abstract

Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs. © 2017, Mary Ann Liebert, Inc.The study was coordinated through the International Zebrafish Neuroscience Research Consortium (ZNRC), and this collaboration was supported by St. Petersburg State University Intramural Research program (DMM, EVK, AVK), Ural Federal University (AVK), Guangdong Ocean University (CS, AVK), the University of Passo Fundo (LJGB), CNPq grant 470260/2013 (LJGB) and CNPq research fellowships 301992/2014-2 (LJGB) and 307595/2015-3 (DBR). The funders had no involvement in the study design, data collection or analysis, and manuscript preparation. AVK is the Chair of ZNRC, and his research is supported by the Russian Foundation for Basic Research (RFBR) grant 16-04-00851. The authors thank Mr Rodrigo Zanandrea (University of Passo Fundo, Brazil) for his assistance with zebrafish cortisol analyses