Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia
Serikuly N. Alpyshov E.T. Wang D. Wang J. Yang L. Hu G. Yan D. Demin K.A. Kolesnikova T.O. Galstyan D. Amstislavskaya T.G. Babashev A.M. Mor M.S. Efimova E.V. Gainetdinov R.R. Strekalova T. de Abreu M.S. Song C. Kalueff A.V.
10 January 2021Elsevier Inc.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
2021#104
Arecoline is a naturally occurring psychoactive alkaloid with partial agonism at nicotinic and muscarinic acetylcholine receptors. Arecoline consumption is widespread, making it the fourth (after alcohol, nicotine and caffeine) most used substance by humans. However, the mechanisms of acute and chronic action of arecoline in-vivo remain poorly understood. Animal models are a valuable tool for CNS disease modeling and drug screening. Complementing rodent studies, the zebrafish (Danio rerio) emerges as a promising novel model organism for neuroscience research. Here, we assessed the effects of acute and chronic arecoline on adult zebrafish behavior and physiology. Overall, acute and chronic arecoline treatments produced overt anxiolytic-like behavior (without affecting general locomotor activity and whole-body cortisol levels), with similar effects also caused by areca nut water extracts. Acute arecoline at 10 mg/L disrupted shoaling, increased social preference, elevated brain norepinephrine and serotonin levels and reduced serotonin turnover. Acute arecoline also upregulated early protooncogenes c-fos and c-jun in the brain, whereas chronic treatment with 1 mg/L elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). Finally, acute 2-h discontinuation of chronic arecoline treatment evoked withdrawal-like anxiogenic behavior in zebrafish. In general, these findings support high sensitivity of zebrafish screens to arecoline and related compounds, and reinforce the growing utility of zebrafish for probing molecular mechanisms of CNS drugs. Our study also suggests that novel anxiolytic drugs can eventually be developed based on arecoline-like molecules, whose integrative mechanisms of CNS action may involve monoaminergic and neuro-immune modulation.
Anxiety , Arecoline , CNS , Genomic effects , Zebrafish
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School of Pharmacy, Southwest University, Chongqing, China
Institute of Experimental Medicine, Almazov National Medical Research Centre, St. Petersburg, Russian Federation
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russian Federation
Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russian Federation
Kazakh National Pedagogigal University, Almaty, Kazakhstan
Bioscience Institute, University of Passo Fundo, Passo Fundo, Brazil
Ural Federal University, Ekaterinburg, Russian Federation
Laboratory of Psychiatric Neurobiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands
Research Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
Guangdong Ocean University, Zhanjiang, China
Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russian Federation
School of Pharmacy
Institute of Experimental Medicine
Institute of Translational Biomedicine
Scientific Research Institute of Physiology and Basic Medicine
Kazakh National Pedagogigal University
Bioscience Institute
Ural Federal University
Laboratory of Psychiatric Neurobiology
Department of Psychiatry and Neuropsychology
Research Institute of General Pathology and Pathophysiology
Guangdong Ocean University
Granov Russian Research Center of Radiology and Surgical Technologies
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