Towards Modeling Anhedonia and Its Treatment in Zebrafish

Mood disorders, especially depression, are a major cause of human disability. The loss of pleasure (anhedonia) is a common, severely debilitating symptom of clinical depression. Experimental animal models are widely used to better understand depression pathogenesis and to develop novel antidepressant therapies. In rodents, various experimental models of anhedonia have already been developed and extensively validated. Complementing rodent studies, the zebrafish (Danio rerio) is emerging as a powerful model organism to assess pathobiological mechanisms of affective disorders, including depression. Here, we critically discuss the potential of zebrafish for modeling anhedonia and studying its molecular mechanisms and translational implications. © 2021 The Author(s). Published by Oxford University Press on behalf of CINP

Modulation of Behavioral and Neurochemical Responses of Adult Zebrafish by Fluoxetine, Eicosapentaenoic Acid and Lipopolysaccharide in the Prolonged Chronic Unpredictable Stress Model

Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism. © 2021, The Author(s).This research was supported solely by the Russian Science Foundation (RSF) grant 19‐15‐00053. K.A.D. is supported by the Special Rector’s Productivity Fellowship for SPSU PhD Students, and the lab is supported by St. Petersburg State University state budgetary funds (project ID 73026081). A.V.K. is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) and President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) that coordinated this collaborative multi-laboratory project. The consortium provided a collaborative idea exchange platform for this study, it is not considered as affiliation and did not fund the study. A.V.K. lab is supported by the Southwest University (SWU) Zebrafish Platform Construction Fund (Chongqing, China). The authors thank Professor Raul R. Gainetdinov (Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia) for his generous assistance with the HPLC studies in his laboratory. The funders had no role in the design, analyses, and interpretation of the submitted study, or decision to publish