Research output: Contribution to journal › Article › peer-review
Effects of acute and chronic arecoline in adult zebrafish : Anxiolytic-like activity, elevated brain monoamines and the potential role of microglia. / Serikuly, Nazar; Alpyshov, Erik T; Wang, DongMei; Wang, JingTao; Yang, LongEn; Hu, GuoJun; Yan, DongNi; Demin, Konstantin A.; Kolesnikova, Tatyana O.; Galstyan, David; Amstislavskaya, Tamara G; Babashev, Abdrazak M.; Mor, Mikael S.; Efimova, Evgeniya V.; Gainetdinov, Raul R; Strekalova, Tatyana; de Abreu, Murilo S; Song, Cai; Kalueff, Allan V.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 104, 109977, 10.01.2021.Research output: Contribution to journal › Article › peer-review
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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, DongMei
AU - Wang, JingTao
AU - Yang, LongEn
AU - Hu, GuoJun
AU - Yan, DongNi
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 produce overt anxiolytic-like behavior without affecting general locomotor activity and whole-body cortisol levels. 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, whereas its chronic treatment elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). 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 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 produce overt anxiolytic-like behavior without affecting general locomotor activity and whole-body cortisol levels. 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, whereas its chronic treatment elevated brain expression of microglia-specific biomarker genes egr2 and ym1 (thus, implicating microglial mechanisms in potential effects of long-term arecoline use). 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 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 - Zebrafish
KW - Arecoline
KW - CNS
KW - Anxiety
KW - Genomic effects
KW - ACTIVATION
KW - NEUROCHEMISTRY
KW - BEHAVIORAL-RESPONSES
KW - INFLAMMATION
KW - RELEVANCE
KW - DYNAMICS
KW - GENE-EXPRESSION
KW - SYSTEMS
KW - STRESS
KW - EXPOSURE
UR - http://www.scopus.com/inward/record.url?scp=85086655523&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/c76401ee-d5e4-3ecc-9c93-3878173eeb79/
U2 - 10.1016/j.pnpbp.2020.109977
DO - 10.1016/j.pnpbp.2020.109977
M3 - Article
C2 - 32454162
VL - 104
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
M1 - 109977
ER -
ID: 53907475