Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish (original) (raw)
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Modeling Stress and Anxiety in Zebrafish
Neuromethods, 2010
While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behaviors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.
Chapter 3 Modeling Stress and Anxiety in Zebrafish
2014
While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behav-iors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.
Behaviour, 2012
Animals encounter stressful situations multiple times throughout their lives and often successfully cope with them. Individuals vary in the nature and intensity of their behavioral and physiological response to stressors, often representing correlated and qualitatively distinct coping styles (e.g., proactive and reactive). These alternative coping styles are ways an animal can overcome a variety of stressful situations, which ultimately can have important fitness consequences. Here we use zebrafish (Danio rerio) recently wild-derived and selectively bred for amount of stationary behavior (High and Low lines) and a classic domesticated strain (AB) to document the utility of these zebrafish strains in understanding coping mechanisms. The Low Stationary Behavior (LSB) line of zebrafish displayed significantly lower stress and anxiety-related behaviors than the High Stationary Behavior (HSB) across six stress and anxiety-related behavioral assays. In some assays, we observed strain differences in behavior within three minutes of the start of the trial. Males also showed reduced levels of anxiety-related behaviors relative to females in two assays. Comparing wild-derived and domesticated strains, the AB line displayed significantly lower levels of anxietyrelated behavior in half of the assays. This study demonstrates that our selectively bred lines from wild-caught zebrafish (HSB, LSB) exhibit consistent and divergent behavioral stress responses across multiple distinct assays. Hence these lines may prove useful in understanding the proximate and ultimate mechanisms of coping with stress and anxiety.
Modeling anxiety using adult zebrafish: A conceptual review
Neuropharmacology, 2012
Zebrafish (Danio rerio) are rapidly emerging as a useful animal model in neurobehavioral research. Mounting evidence shows the suitability of zebrafish to model various aspects of anxiety-related states. Here, we evaluate established and novel approaches to uncover the molecular substrates, genetic pathways and neural circuits of anxiety using adult zebrafish. Experimental approaches to modeling anxiety in zebrafish include novelty-based paradigms, pharmacological and genetic manipulations, as well as innovative video-tracking, 3D-reconstructions, bioinformatics-based searchable databases and omics-based tools. Complementing traditional rodent models of anxiety, we provide a conceptual framework for the wider application of zebrafish and other aquatic models in anxiety research.
Pharmacological modulation of anxiety-like phenotypes in adult zebrafish behavioral models
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2011
Zebrafish (Danio rerio) are becoming increasingly popular in neurobehavioral research. Here, we summarize recent data on behavioral responses of adult zebrafish to a wide spectrum of putative anxiolytic and anxiogenic agents. Using the novel tank test as a sensitive and efficient behavioral assay, zebrafish anxiety-like behavior can be bi-directionally modulated by drugs affecting the gamma-aminobutyric acid, monoaminergic, cholinergic, glutamatergic and opioidergic systems. Complementing human and rodent data, zebrafish drugevoked phenotypes obtained in this test support this species as a useful model for neurobehavioral and psychopharmacological research.
Measuring anxiety in zebrafish: A critical review
Zebrafish are increasingly being used in behavioral neuroscience, neuropsychopharmacology and neurotoxicology. Recently, behavioral screens used to model anxiety in rodents were adapted to this species, and novel models which tap on zebrafish behavioral ecology have emerged. However, model-building is an arduous task in experimental psychopathology, and a continuous effort to assess the validity of these measurements is being chased among some researchers. To consider a model as valid, it must possess face, pre-dictive and / or construct validity. In this article, we first review some notions of validity, arguing that, at its limit, face and predictive validity reduce to construct validity. Then we review some procedures which have been used to study anxiety, fear or related processes in zebrafish, using the validity framework. We conclude that, although the predictive validity of some of these models is increasingly being met, there is still a long way in reaching the desired level of construct validity. The refinement of models is an ongoing activity, and behavioral validation and parametric research ought to advance that objective.
Measuring behavioral and endocrine responses to novelty stress in adult zebrafish
Nature Protocols, 2010
several behavioral assays are currently used for high-throughput neurophenotyping and screening of genetic mutations and psychotropic drugs in zebrafish (Danio rerio). In this protocol, we describe a battery of two assays to characterize anxiety-related behavioral and endocrine phenotypes in adult zebrafish. Here, we detail how to use the 'novel tank' test to assess behavioral indices of anxiety (including reduced exploration, increased freezing behavior and erratic movement), which are quantifiable using manual registration and computer-aided video-tracking analyses. In addition, we describe how to analyze whole-body zebrafish cortisol concentrations that correspond to their behavior in the novel tank test. this protocol is an easy, inexpensive and effective alternative to other methods of measuring stress responses in zebrafish, thus enabling the rapid acquisition and analysis of large amounts of data. as will be shown here, fish anxiety-like behavior can be either attenuated or exaggerated depending on stress or drug exposure, with cortisol levels generally expected to parallel anxiety behaviors. this protocol can be completed over the course of 2 d, with a variable testing duration depending on the number of fish used.
Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests
Zebrafish, 2017
Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT a...
Scientific Reports
Larval zebrafish (Danio rerio) has the potential to supplement rodent models due to the availability of resource-efficient, high-throughput screening and high-resolution imaging techniques. Although behavioural models are available in larvae, only a few can be employed to assess anxiety. Here we present the swimming plus-maze (SPM) test paradigm, a tool to assess anxiety-related avoidance of shallow water bodies in early developmental stages. The "+" shaped apparatus consists of arms of different depth, representing different levels of aversiveness similarly to the rodent elevated plus-maze. The paradigm was validated (i) in larval and juvenile zebrafish, (ii) after administration of compounds affecting anxiety and (iii) in differentially aversive experimental conditions. Furthermore, we compared the SPM with conventional "anxiety tests" of zebrafish to identify their shared characteristics. We have clarified that the preference of deeper arms is ontogenetically conserved and can be abolished by anxiolytic or enhanced by anxiogenic agents, respectively. The behavioural readout is insensitive to environmental aversiveness and is unrelated to behaviours assessed by conventional tests involving young zebrafish. Taken together, we have developed a sensitive high-throughput test allowing the assessment of anxiety-related responses of zebrafish regardless of developmental stage, granting the opportunity to combine larva-based state-of-the-art methods with detailed behavioral analysis.
PloS one, 2012
Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of group and individually housed fish, and found that individually housed individuals have lower basal cortisol levels. In our second experiment we found ethanol appeared to have an anxiolytic effect with individually housed fish but not those that were group housed. In our final experiment, we examined the effects of changing the fishes' water prior to tank diving as an additional acclimation procedure. We found that this had no effect on individually housed fish, but appeared to affect the typical tank diving responses of the group housed individuals. In conclusion, we demonstrate that housing represents an important factor in obtaining reliable data from this methodology, and should be considered by researchers interested in comparative models of anxiety in zebrafish in order to refine their approach and to increase the power in their experiments.