Measures of Anxiety in Zebrafish (Danio rerio): Dissociation of Black/White Preference and Novel Tank Test

The effects of wall color stimuli on diving, and the effects of depth stimuli on scototaxis, were assessed in zebrafish. Three groups of fish were confined to a black, a white, or a transparent tank, and tested for depth preference. Two groups of fish were confined to a deep or a shallow tank, and tested for black-white preference. As predicted, fish preferred the deep half of a split-tank over the shallow half, and preferred the black half of a black/white tank over the white half. Results indicated that the tank wall color significantly affected depth preference, with the transparent tank producing the strongest depth preference and the black tank producing the weakest preference. Tank depth, however, did not significantly affect color preference. Additionally, wall color significantly affected shuttling and immobility, while depth significantly affected shuttling and thigmotaxis. These results are consistent with previous indications that the diving response and scototaxis may reflect dissociable mechanisms of behavior. We conclude that the two tests are complementary rather than interchangeable, and that further research on the motivational systems underlying behavior in each of the two tests is needed

Zebrafish models for attention deficit hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a common, debilitating neurodevelopmental disorder associated with inattentiveness, pathological hyperactivity and impulsivity. Despite the mounting human and animal evidence, the neurological pathways underlying ADHD remain poorly understood. Novel translational model organisms, such as the zebrafish (Danio rerio), are becoming important tools to investigate genetic and pathophysiological mechanisms of various neuropsychiatric disorders. Here, we discuss ADHD etiology, existing animal models and their limitations, and emphasize the advantages of using zebrafish to model ADHD. Overall, the growing utility of zebrafish models may improve our understanding of ADHD and facilitate drug discovery to prevent or treat this disorder. © 2019 Elsevier Lt

Naloxone Prolongs Abdominal Constriction Writhing-Like Behavior in a Zebrafish-Based Pain Model

The ability to detect noxious stimuli is essential to survival. However, pathological pain is maladaptive and severely debilitating. Endogenous and exogenous opioids modulate pain responses via opioid receptors, reducing pain sensibility. Due to the high genetic and physiological similarities to rodents and humans, the zebrafish is a valuable tool to assess pain responses and the underlying mechanisms involved in nociception. Although morphine attenuates pain-like responses of zebrafish, there are no data showing if the antagonism of opioid receptors prolongs pain duration in the absence of an exogenous opioid. Here, we investigated whether a common opioid antagonist naloxone affects the abdominal constriction writhing-like response, recently characterized as a zebrafish-based pain behavior. Animals were injected intraperitoneally with acetic acid (5.0%), naloxone (1.25 mg/kg; 2.5 mg/kg; 5.0 mg/kg) or acetic acid with naloxone to investigate the changes in their body curvature for 1 h. Acetic acid elicited a robust pain-like response in zebrafish, as assessed by aberrant abdominal body curvature, while no effects were observed following PBS injection. Although naloxone alone did not alter the frequency and duration of this behavior, it dose-dependently prolonged acetic acid-induced abdominal curvature response. Besides reinforcing the use of the abdominal writhing-like phenotype as a behavioral endpoint to measure acute pain responses in zebrafish models, our novel data suggest a putative role of endogenous opioids in modulating the recovery from pain stimulation in zebrafish. © 2019 Elsevier B.V.We recognize the financial support and fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) . F.V.C. was recipient of CAPES fellowship. J.C. and F.V.S. receive the CNPq fellowship. D.B.R. is a recipient of CNPq research productivity grant ( 305051/2018-0 ) and his work is also supported by the PROEX/CAPES (process number 23038.005848/2018-31) and PRONEM/FAPERGS (process number 16/2551-0000248-7) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 19-15-00053. All authors contributed to the preparation of the manuscript and approved its final version. The funders had no influence on the study design, collection, analysis, and interpretation of data, as well as on writing and submission of this manuscript

Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests

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 and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs