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

Exploring CNS Effects of American Traditional Medicines using Zebrafish Models

Although American traditional medicine (ATM) has been practiced for millennia, its complex multi-target mechanisms of therapeutic action remain poorly understood. Animal models are widely used to elucidate the therapeutic effects of various ATMs, including their modulation of brain and behavior. Complementing rodent models, the zebrafish (Danio rerio) is a promising novel organism in translational neuroscience and neuropharmacology research. Here, we emphasize the growing value of zebrafish for testing neurotropic effects of ATMs and outline future directions of research in this field. We also demonstrate the developing utility of zebrafish as complementary models for probing CNS mechanisms of ATM action and their potential to treat brain disorders. © 2022 Bentham Science Publishers.Applied Genetics MIPT, (075-15-2021-684)International Zebrafish Neurosci-ence Research ConsortiumSirius UniversitySouthwest University Zebrafish Platform Construction Funds (Chongqing, ChinaZNRCConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, (305051/2018-0)Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, (19/2551-0001-669-7, 19/2551-0001764-2)Russian Science Foundation, RSF, (20-65-46006)The study is supported by the Southwest University Zebrafish Platform Construction Funds (Chongqing, China). AVK is the Chair of the International Zebrafish Neurosci-ence Research Consortium (ZNRC) that coordinated this collaborative project. DBR receives the CNPq research productivity grant (process 305051/2018-0) and the FAPERGS “Gaucho” Researcher Program – PQG fellowship grant (process 19/2551-0001764-2). ACVVG is supported by the FAPERGS research fellowships 19/2551-0001-669-7. The study is partly supported by Sirius University (Sochi, Russia). Research collaboration here is supported by the Russian Science Foundation (RSF) grant 20-65-46006 to Prof. T.G. Amstislavskaya. The funders had no role in the design, analyses, and interpretation of the submitted study or the decision to publish. The study used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684)

The Use of Zebrafish as a Non-traditional Model Organism in Translational Pain Research: The Knowns and the Unknowns

The ability of the nervous system to detect a wide range of noxious stimuli is crucial to avoid life-threatening injury and to trigger protective behavioral and physiological responses. Pain represents a complex phenomenon, including nociception associated with cognitive and emotional processing. Animal experimental models have been developed to understand the mechanisms involved in pain response, as well as to discover novel pharmacological and non-pharmacological anti-pain therapies. Due to the genetic tractability, similar physiology, low cost, and rich behavioral repertoire, the zebrafish (Danio rerio) is a powerful aquatic model for modeling pain responses. Here, we summarize the molecular machinery of zebrafish responses to painful stimuli, as well as emphasize how zebrafish-based pain models have been successfully used to understand specific molecular, physiological, and behavioral changes following different algogens and/or noxious stimuli (e.g., acetic acid, formalin, histamine, Complete Freund's Adjuvant, cinnamaldehyde, allyl isothiocyanate, and fin clipping). We also discuss recent advances in zebrafish-based studies and outline the potential advantages and limitations of the existing models to examine the mechanisms underlying pain responses from evolutionary and translational perspectives. Finally, we outline how zebrafish models can represent emergent tools to explore pain behaviors and pain-related mood disorders, as well as to facilitate analgesic therapy screening in translational pain research. © 2022 Bentham Science Publishers.International Zebrafish Neuroscience Research Con sortiumPROEX, (23038.005450/2020-19)Sirius UniversityZNRCCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPESConselho Nacional de Desenvolvimento Científico e Tecnológico, CNPqFundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, FAPERGS, (19/2551-0001764-2)Russian Science Foundation, RSF, (20-65-46006)National Centre for the Replacement Refinement and Reduction of Animals in Research, NC3RsFunding text 1: F.V.C., V.A.Q., and L.C.R. received CAPES fellowship. D.B.R. and A.R.S. are recipients of CNPq research productivity grant. D.B.R. research is also supported by PROEX/CAPES (process number 23038.005450/2020-19) and Programa PQ-Gaúcho FAPERGS (process number 19/2551-0001764-2) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Con-Funding text 2: F.V.C., V.A.Q., and L.C.R. received CAPES fellowship. D.B.R. and A.R.S. are recipients of CNPq research productivity grant. D.B.R. research is also supported by PROEX/CAPES (process number 23038.005450/2020-19) and Programa PQ-Ga?cho FAPERGS (process number 19/2551-0001764-2) fellowship grants. A.V.K. is the Chair of the International Zebrafish Neuroscience Research Con sortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 20-65-46006. L.U.S. is convenor of the FELASA working group producing a report on Pain Management in Zebrafish and is a member of the NC3Rs (UK) expert panel on zebrafish welfare. The funders did not influence writing and submission of this manuscript.Funding text 3: sortium (ZNRC). His research is supported by the Russian Science Foundation (RSF) grant 20-65-46006. L.U.S. is convenor of the FELASA working group producing a report on Pain Management in Zebrafish and is a member of the NC3Rs (UK) expert panel on zebrafish welfare. The funders did not influence writing and submission of this manuscript.Funding text 4: The authors thank the financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Finance Code 001, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). AVK collaboration is supported by Sirius University, Sochi, Russia