@article{f689485302a64c79b31343b49ccc03ae,
title = "Effects of acute and chronic arecoline in adult zebrafish: Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia",
abstract = "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.",
keywords = "activation, anxiety, arecoline, behavioral-responses, cns, dynamics, exposure, gene-expression, genomic effects, inflammation, neurochemistry, relevance, stress, systems, zebrafish, ACTIVATION, CNS, NEUROCHEMISTRY, BEHAVIORAL-RESPONSES, GENE-EXPRESSION, Anxiety, STRESS, EXPOSURE, Zebrafish, Arecoline, Genomic effects, INFLAMMATION, RELEVANCE, DYNAMICS, SYSTEMS",
author = "N. Serikuly and E.T. Alpyshov and D.M. Wang and J.T. Wang and L.E. Yang and G.J. Hu and D.N. Yan and K.A. Demin and T.O. Kolesnikova and D. Galstyan and T.G. Amstislavskaya and A.M. Babashev and M.S. Mor and E.V. Efimova and R.R. Gainetdinov and T. Strekalova and {de Abreu}, M.S. and C. Song and A.V. Kalueff",
note = "Funding Information: This study is supported by the Southwest University Zebrafish Platform Construction Funds. AVK is the Chair of the International Zebrafish Neuroscience Consortium (ZNRC) that coordinated this collaborative study. KAD is supported by the President of Russia Graduate Fellowship and the Special Rector's Productivity Fellowship for SPSU PhD Students. The laboratory project is supported by Russian Science Foundation grant 19-15-00053 . KAD, DSG and TOK are supported by the project 51130521 of St. Petersburg State University (St. Petersburg, Russia). TGA is supported by the budgetary state funding for basic research from the Institute of Physiology and Basic Medicine (Novosibirsk, Russia) project AAAA-A16-116021010228-0. RRG, EVE and MSM are supported by the project 51143531 of St. Petersburg State University. The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish. The authors declare no conflicts of interest. Funding Information: This study is supported by the Southwest University Zebrafish Platform Construction Funds. AVK is the Chair of the International Zebrafish Neuroscience Consortium (ZNRC) that coordinated this collaborative study. KAD is supported by the President of Russia Graduate Fellowship and the Special Rector's Productivity Fellowship for SPSU PhD Students. The laboratory project is supported by Russian Science Foundation grant 19-15-00053. KAD, DSG and TOK are supported by the project 51130521 of St. Petersburg State University (St. Petersburg, Russia). TGA is supported by the budgetary state funding for basic research from the Institute of Physiology and Basic Medicine (Novosibirsk, Russia) project AAAA-A16-116021010228-0. RRG, EVE and MSM are supported by the project 51143531 of St. Petersburg State University. The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "10",
doi = "10.1016/j.pnpbp.2020.109977",
language = "English",
volume = "104",
journal = "Progress in Neuro-Psychopharmacology & Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Science",
}