TY - JOUR
T1 - Effects of acute and chronic arecoline in adult zebrafish
T2 - Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia
AU - Serikuly, Nazar
AU - Alpyshov, Erik T.
AU - Wang, Dong Mei
AU - Wang, Jing Tao
AU - Yang, Long En
AU - Hu, Guo Jun
AU - Yan, Dong Ni
AU - Demin, Konstantin A.
AU - Kolesnikova, Tatyana O.
AU - Galstyan, David
AU - Amstislavskaya, Tamara G.
AU - Babashev, Abdrazak M.
AU - Mor, Mikael S.
AU - Efimova, Evgeniya V.
AU - Gainetdinov, Raul R.
AU - Strekalova, Tatyana
AU - de Abreu, Murilo S.
AU - Song, Cai
AU - Kalueff, Allan V.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1/10
Y1 - 2021/1/10
N2 - 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.
AB - 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.
KW - Anxiety
KW - Arecoline
KW - CNS
KW - Genomic effects
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85086655523&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2020.109977
DO - 10.1016/j.pnpbp.2020.109977
M3 - Article
C2 - 32454162
AN - SCOPUS:85086655523
SN - 0278-5846
VL - 104
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 109977
ER -