The zebrafish (Danio rerio) has emerged as a model species for translational research in various neuroscience areas, including depressive disorders. Because of their physiological (neuroanatomical, neuroendocrine, neurochemical) and genetic homology to mammals, robust phenotypes, and value in high-throughput genetic and chemical genetic screens, zebrafish are ideal for developing valid experimental models of major depression and discovering novel therapeutics. Behavioral testing approaches, such as approach-avoidance, cognitive, and social paradigms, are available in zebrafish and have utility in identifying depression-like indices in zebrafish in response to physiological, genetic, environmental, and/or psychopharmacological alterations. In addition, the high sensitivity of zebrafish to commonly prescribed psychotropic drugs supports the use of this model as an invaluable tool for pharmacological research and drug screening. This Review outlines the benefits of using the zebrafish model for depression studies and summarizes the current research in this field.
