TY - JOUR

T1 - The zebrafish tail immobilization (ZTI) test as a new tool to assess stress-related behavior and a potential screen for drugs affecting despair-like states

AU - Demin, Konstantin A.

AU - Lakstygal, Anton M.

AU - Chernysh, Maria V.

AU - Krotova, Natalia A.

AU - Taranov, Aleksandr S.

AU - Ilyin, Nikita P.

AU - Seredinskaya, Maria V.

AU - Tagawa, Natsuki

AU - Savva, Anna K.

AU - Mor, Mikael S.

AU - Vasyutina, Marina L.

AU - Efimova, Evgeniya V.

AU - Kolesnikova, Tatyana O.

AU - Gainetdinov, Raul R.

AU - Strekalova, Tatyana

AU - Amstislavskaya, Tamara G.

AU - de Abreu, Murilo S.

AU - Kalueff, Allan V.

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - Behavioral despair

KW - Depression

KW - Drug screening

KW - Immobilization

KW - Zebrafish

KW - ACUTE RESTRAINT STRESS

KW - ASSESSING ANTIDEPRESSANT ACTIVITY

KW - CHRONIC MILD STRESS

KW - FORCED SWIM TEST

KW - ADULT ZEBRAFISH

KW - ANXIETY-LIKE BEHAVIOR

KW - SUSPENSION TEST

KW - DEPRESSION-LIKE BEHAVIOR

KW - ANIMAL-MODELS

KW - METHYL-D-ASPARTATE

UR - http://www.scopus.com/inward/record.url?scp=85080113697&partnerID=8YFLogxK

U2 - 10.1016/j.jneumeth.2020.108637

DO - 10.1016/j.jneumeth.2020.108637

M3 - Article

C2 - 32081675

AN - SCOPUS:85080113697

VL - 337

JO - Journal of Neuroscience Methods

JF - Journal of Neuroscience Methods

SN - 0165-0270

M1 - 108637

ER -