PUBLICATION
An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish
- Authors
- Giacomini, A.C., Bueno, B.W., Marcon, L., Scolari, N., Genario, R., Demin, K.A., Kolesnikova, T.O., Kalueff, A.V., de Abreu, M.S.
- ID
- ZDB-PUB-200829-2
- Date
- 2020
- Source
- Journal of psychopharmacology (Oxford, England) 34(12): 1449-1456 (Journal)
- Registered Authors
- Keywords
- Donepezil, acetylcholinesterase inhibitor, anxiety, cortisol, zebrafish
- MeSH Terms
-
- Animals
- Anxiety/drug therapy*
- Anxiety/metabolism*
- Behavior, Animal/drug effects*
- Cholinesterase Inhibitors/administration & dosage
- Cholinesterase Inhibitors/pharmacology*
- Disease Models, Animal
- Donepezil/administration & dosage
- Donepezil/pharmacology*
- Female
- Hydrocortisone/metabolism*
- Locomotion/drug effects*
- Male
- Zebrafish
- PubMed
- 32854587 Full text @ J. Psychopharmacol. (Oxford)
Citation
Giacomini, A.C., Bueno, B.W., Marcon, L., Scolari, N., Genario, R., Demin, K.A., Kolesnikova, T.O., Kalueff, A.V., de Abreu, M.S. (2020) An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish. Journal of psychopharmacology (Oxford, England). 34(12):1449-1456.
Abstract
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.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
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