TY - JOUR

T1 - Unconventional anxiety pharmacology in zebrafish

T2 - 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 - 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

KW - SOCIAL-INTERACTION TEST

KW - NICOTINIC ACETYLCHOLINE-RECEPTORS

KW - ELEVATED PLUS-MAZE

KW - MU-OPIOID RECEPTOR

KW - BRAIN-SEROTONIN TURNOVER

KW - LYSERGIC-ACID DIETHYLAMIDE

KW - INDIVIDUAL-DIFFERENCES

KW - BEHAVIORAL-RESPONSES

KW - ANIMAL-MODELS

KW - NEUROSCIENCE RESEARCH

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

VL - 207

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

SN - 0091-3057

M1 - 173205

ER -