Research output: Contribution to journal › Article › peer-review
An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish. / Giacomini, Ana CVV; Bueno, Barbara W; Marcon, Leticia; Scolari, Naiara; Genario, Rafael; Demin, Konstantin A; Kolesnikova, Tatyana O; Kalueff, Allan V; de Abreu, Murilo S.
In: Journal of Psychopharmacology, Vol. 34, No. 12, 0269881120944155, 12.2020, p. 1449-1456.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 61797874