TY - JOUR

T1 - Unconventional anxiety pharmacology in zebrafish: Drugs beyond traditional anxiogenic and anxiolytic spectra

AU - de Abreu, Murilo S.

AU - Giacomini, Ana C.V.V.

AU - Demin, Konstantin A.

AU - Galstyan, David S.

AU - Zabegalov, Konstantin N.

AU - Kolesnikova, Tatyana O.

AU - Amstislavskaya, Tamara G.

AU - Strekalova, Tatyana

AU - Petersen, Elena V.

AU - Kalueff, Allan V.

N1 - Funding Information: This study is supported by the Southwest University Zebrafish Platform Construction Funds. AVK is the President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) that coordinated this collaborative project. KAD is supported by the Special Rector's Fellowship for SPSU PhD Students, and state budgetary research project 51130521 from SPSU. The laboratory is supported by the budgetary state funding from the Ministry of Healthcare of Russian Federation (project 121040200141-4). ACVVG is supported by the Research Support Foundation of the State of Rio Grande do Sul (FAPERGS) research fellowships 19/2551-0001-669-7. TGA is supported by the Russian Science Foundation (RSF) grant 20-65-46006. KNZ was supported by the Academic Mobility Program (Act 211 of the Government of Russian Federation) contract 02.A03.21.0006. The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish. The authors declare no conflicts of interest. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/8

Y1 - 2021/8

N2 - Anxiety is the most prevalent brain disorder and a common cause of human disability. Animal models are critical for understanding anxiety pathogenesis and its pharmacotherapy. The zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in anxiety research and anxiolytic drug screening. High similarity between human, rodent and zebrafish molecular targets implies shared signaling pathways involved in anxiety pathogenesis. However, mounting evidence shows that zebrafish behavior can be modulated by drugs beyond conventional anxiolytics or anxiogenics. Furthermore, these effects may differ from human and/or rodent responses, as such ‘unconventional’ drugs may affect zebrafish behavior despite having no such profiles (or exerting opposite effects) in humans or rodents. Here, we discuss the effects of several putative unconventional anxiotropic drugs (aspirin, lysergic acid diethylamide (LSD), nicotine, naloxone and naltrexone) and their potential mechanisms of action in zebrafish. Emphasizing the growing utility of zebrafish models in CNS drug discovery, such unconventional anxiety pharmacology may provide important, evolutionarily relevant insights into complex regulation of anxiety in biological systems. Albeit seemingly complicating direct translation from zebrafish into clinical phenotypes, this knowledge may instead foster the development of novel CNS drugs, eventually facilitating innovative treatment of patients based on novel ‘unconventional’ targets identified in fish models.

AB - Anxiety is the most prevalent brain disorder and a common cause of human disability. Animal models are critical for understanding anxiety pathogenesis and its pharmacotherapy. The zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in anxiety research and anxiolytic drug screening. High similarity between human, rodent and zebrafish molecular targets implies shared signaling pathways involved in anxiety pathogenesis. However, mounting evidence shows that zebrafish behavior can be modulated by drugs beyond conventional anxiolytics or anxiogenics. Furthermore, these effects may differ from human and/or rodent responses, as such ‘unconventional’ drugs may affect zebrafish behavior despite having no such profiles (or exerting opposite effects) in humans or rodents. Here, we discuss the effects of several putative unconventional anxiotropic drugs (aspirin, lysergic acid diethylamide (LSD), nicotine, naloxone and naltrexone) and their potential mechanisms of action in zebrafish. Emphasizing the growing utility of zebrafish models in CNS drug discovery, such unconventional anxiety pharmacology may provide important, evolutionarily relevant insights into complex regulation of anxiety in biological systems. Albeit seemingly complicating direct translation from zebrafish into clinical phenotypes, this knowledge may instead foster the development of novel CNS drugs, eventually facilitating innovative treatment of patients based on novel ‘unconventional’ targets identified in fish models.

KW - Anxiogenic

KW - Anxiolytic

KW - Atypical responses

KW - Pharmacotherapy

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85109007926&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/79cad3ec-0b42-3d97-b1ae-cbea59974a0a/

U2 - 10.1016/j.pbb.2021.173205

DO - 10.1016/j.pbb.2021.173205

M3 - Review article

C2 - 33991579

AN - SCOPUS:85109007926

VL - 207

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

M1 - 173205

ER -