PUBLICATION

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

Authors
Demin, K.A., Lakstygal, A.M., Chernysh, M.V., Krotova, N.A., Taranov, A.S., Ilyin, N.P., Seredinskaya, M.V., Tagawa, N., Savva, A.K., Mor, M.S., Vasyutina, M.L., Efimova, E.V., Kolesnikova, T.O., Gainetdinov, R.R., Strekalova, T., Amstislavskaya, T.G., de Abreu, M.S., Kalueff, A.V.
ID
ZDB-PUB-200225-9
Date
2020
Source
Journal of Neuroscience Methods   337: 108637 (Journal)
Registered Authors
Kalueff, Allan V.
Keywords
behavioral despair, depression, drug screening, immobilization, zebrafish
MeSH Terms
  • Animals
  • Anxiety/drug therapy
  • Behavior, Animal
  • Disease Models, Animal
  • Motor Activity
  • Pharmaceutical Preparations*
  • Zebrafish*
PubMed
32081675 Full text @ J. Neurosci. Methods
Abstract
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 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 no clear-cut despair-like models in zebrafish.
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 in the small beaker with water.
To validate this model, we used exposure to low-voltage electric shock, alarm pheromone, antidepressants (sertraline and amitriptyline) and an anxiolytic 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, 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.
The ZTI test is the first despair-like experimental model in zebrafish.
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.
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