期刊
JOURNAL OF PSYCHOPHARMACOLOGY
卷 34, 期 12, 页码 1449-1456出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0269881120944155
关键词
Donepezil; zebrafish; cortisol; anxiety; acetylcholinesterase inhibitor
资金
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [17/2551-0001-269-0]
- Southwest University Zebrafish Platform Construction Funds
- Russia Graduate Fellowship
- St. Petersburg State University (SPSU) Rector's Productivity PhD Fellowship
- Russian Science Foundation (RSF) [19-15-00053]
- [51130521]
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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