Konstantin A Demin1, Anton M Lakstygal2, Maria V Chernysh3, Natalia A Krotova4, Aleksandr S Taranov3, Nikita P Ilyin3, Maria V Seredinskaya3, Natsuki Tagawa5, Anna K Savva6, Mikael S Mor3, Marina L Vasyutina7, Evgeniya V Efimova3, Tatyana O Kolesnikova3, Raul R Gainetdinov3, Tatyana Strekalova8, Tamara G Amstislavskaya9, Murilo S de Abreu10, Allan V Kalueff11. 1. Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. Electronic address: deminkasci@gmail.com. 2. Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Laboratory of Preclinical Bioscreening, Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, Pesochny, Russia. 3. Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. 4. Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. 5. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan. 6. Laboratory of Insect Biopharmacology and Immunology, Faculty of Biology, St. Petersburg State University, St. Petersburg, Russia. 7. Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia. 8. I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Maastricht University, Maastricht, The Netherlands; Research Institute of General Pathology and Pathophysiology, Moscow, Russia. 9. Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia. 10. Bioscience Institute, University of Passo Fundo, Passo Fundo, Brazil. 11. School of Pharmacy, Southwest University, Chongqing, China; Ural Federal University, Ekaterinburg, Russia. Electronic address: avkalueff@gmail.com.
Abstract
BACKGROUND: Affective disorders, especially depression and anxiety, are highly prevalent, debilitating mental illnesses. Animal experimental models are a valuable tool in translational affective neuroscience research. A hallmark phenotype of clinical and experimental depression, the learned helplessness, has become a key target for 'behavioral despair'-based animal models of depression. The zebrafish (Danio rerio) has recently emerged as a promising novel organism for affective disease modeling and CNS drug screening. Despite being widely used to assess stress and anxiety-like behaviors, there are presently no clear-cut despair-like models in zebrafish. NEW METHOD: Here, we introduce a novel behavioral paradigm, the zebrafish tail immobilization (ZTI) test, as a potential tool to assess zebrafish despair-like behavior. Conceptually similar to rodent 'despair' models, the ZTI protocol involves immobilizing the caudal half of the fish body for 5 min, leaving the cranial part to move freely, suspended vertically in a small beaker with water. RESULTS: To validate this model, we used exposure to low-voltage electric shock, alarm pheromone, selected antidepressants (sertraline and amitriptyline) and an anxiolytic drug benzodiazepine (phenazepam), assessing the number of mobility episodes, time spent 'moving', total distance moved and other activity measures of the cranial part of the body, using video-tracking. Both electric shock and alarm pheromone decreased zebrafish activity in this test, antidepressants increased it, and phenazepam was inactive. Furthermore, a 5-min ZTI exposure increased serotonin turnover, elevating the 5-hydroxyindoleacetic acid/serotonin ratio in zebrafish brain, while electric shock prior to ZTI elevated both this and the 3,4-dihydroxyphenylacetic acid/dopamine ratios. In contrast, preexposure to antidepressants sertraline and amitriptyline lowered both ratios, compared to the ZTI test-exposed fish. COMPARISON WITH EXISTINGMETHOD(S): The ZTI test is the first despair-like experimental model in zebrafish. CONCLUSIONS: Collectively, this study suggests the ZTI test as a potentially useful protocol to assess stress-/despair-related behaviors, potentially relevant to CNS drug screening and behavioral phenotyping of zebrafish.
BACKGROUND:Affective disorders, especially depression and anxiety, are highly prevalent, debilitating mental illnesses. Animal experimental models are a valuable tool in translational affective neuroscience research. A hallmark phenotype of clinical and experimental depression, the learned helplessness, has become a key target for 'behavioral despair'-based animal models of depression. The zebrafish (Danio rerio) has recently emerged as a promising novel organism for affective disease modeling and CNS drug screening. Despite being widely used to assess stress and anxiety-like behaviors, there are presently no clear-cut despair-like models in zebrafish. NEW METHOD: Here, we introduce a novel behavioral paradigm, the zebrafish tail immobilization (ZTI) test, as a potential tool to assess zebrafish despair-like behavior. Conceptually similar to rodent 'despair' models, the ZTI protocol involves immobilizing the caudal half of the fish body for 5 min, leaving the cranial part to move freely, suspended vertically in a small beaker with water. RESULTS: To validate this model, we used exposure to low-voltage electric shock, alarm pheromone, selected antidepressants (sertraline and amitriptyline) and an anxiolytic drug benzodiazepine (phenazepam), assessing the number of mobility episodes, time spent 'moving', total distance moved and other activity measures of the cranial part of the body, using video-tracking. Both electric shock and alarm pheromone decreased zebrafish activity in this test, antidepressants increased it, and phenazepam was inactive. Furthermore, a 5-min ZTI exposure increased serotonin turnover, elevating the 5-hydroxyindoleacetic acid/serotonin ratio in zebrafish brain, while electric shock prior to ZTI elevated both this and the 3,4-dihydroxyphenylacetic acid/dopamine ratios. In contrast, preexposure to antidepressants sertraline and amitriptyline lowered both ratios, compared to the ZTI test-exposed fish. COMPARISON WITH EXISTINGMETHOD(S): The ZTI test is the first despair-like experimental model in zebrafish. CONCLUSIONS: Collectively, this study suggests the ZTI test as a potentially useful protocol to assess stress-/despair-related behaviors, potentially relevant to CNS drug screening and behavioral phenotyping of zebrafish.
Authors: Aaron C Ericsson; Susheel B Busi; Daniel J Davis; Henda Nabli; David C Eckhoff; Rebecca A Dorfmeyer; Giedre Turner; Payton S Oswalt; Marcus J Crim; Elizabeth C Bryda Journal: Anim Microbiome Date: 2021-08-05
Authors: Konstantin A Demin; Anton M Lakstygal; Nataliya A Krotova; Alexey Masharsky; Natsuki Tagawa; Maria V Chernysh; Nikita P Ilyin; Alexander S Taranov; David S Galstyan; Ksenia A Derzhavina; Nataliia A Levchenko; Tatiana O Kolesnikova; Mikael S Mor; Marina L Vasyutina; Evgeniya V Efimova; Nataliia Katolikova; Andrey D Prjibelski; Raul R Gainetdinov; Murilo S de Abreu; Tamara G Amstislavskaya; Tatyana Strekalova; Allan V Kalueff Journal: Sci Rep Date: 2020-11-17 Impact factor: 4.379
Authors: Konstantin A Demin; Tatiana O Kolesnikova; David S Galstyan; Nataliya A Krotova; Nikita P Ilyin; Ksenia A Derzhavina; Nataliia A Levchenko; Tatyana Strekalova; Murilo S de Abreu; Elena V Petersen; Maria Seredinskaya; Yulia V Cherneyko; Yuriy M Kositsyn; Dmitry V Sorokin; Konstantin N Zabegalov; Mikael S Mor; Evgeniya V Efimova; Allan V Kalueff Journal: Sci Rep Date: 2021-07-12 Impact factor: 4.379