TY - JOUR

T1 - An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

AU - Giacomini, Ana CVV

AU - Bueno, Barbara W

AU - Marcon, Leticia

AU - Scolari, Naiara

AU - Genario, Rafael

AU - Demin, Konstantin A

AU - Kolesnikova, Tatyana O

AU - Kalueff, Allan V

AU - de Abreu, Murilo S

N1 - Publisher Copyright: © The Author(s) 2020.

PY - 2020/12

Y1 - 2020/12

N2 - BACKGROUND: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening.AIM: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish.METHODS: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels.RESULTS: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses.CONCLUSION: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

AB - BACKGROUND: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening.AIM: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish.METHODS: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels.RESULTS: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses.CONCLUSION: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

KW - Donepezil

KW - zebrafish

KW - cortisol

KW - anxiety

KW - ACETYLCHOLINESTERASE INHIBITORS

KW - acetylcholinesterase inhibitor

KW - CORTICOSTERONE

KW - BRAIN ACETYLCHOLINE

KW - PERFORMANCE

KW - PHYSOSTIGMINE

KW - YOUNG

KW - BEHAVIORAL-RESPONSES

KW - MEMORY

KW - DISEASE

KW - INDUCED DEFICITS

KW - STRESS

UR - http://www.scopus.com/inward/record.url?scp=85089964766&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/8c2011ce-fa68-3a9d-b43c-70244774069a/

U2 - 10.1177/0269881120944155

DO - 10.1177/0269881120944155

M3 - Article

C2 - 32854587

VL - 34

SP - 1449

EP - 1456

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

SN - 0269-8811

IS - 12

M1 - 0269881120944155

ER -