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

Ana CVV Giacomini, Barbara W Bueno, Leticia Marcon, Naiara Scolari, Rafael Genario, Konstantin A Demin, Tatyana O Kolesnikova, Allan V Kalueff, Murilo S de Abreu

Research output

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.

Original languageEnglish
JournalJournal of Psychopharmacology
DOIs
Publication statusE-pub ahead of print - 27 Aug 2020

Fingerprint Dive into the research topics of 'An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish'. Together they form a unique fingerprint.

  • Cite this

    Giacomini, A. CVV., 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. https://doi.org/10.1177/0269881120944155