TY - JOUR
T1 - Behavioral and physiological effects of acute and chronic kava exposure in adult zebrafish
AU - Wang, Dongmei
AU - Yang, Long En
AU - Wang, Jingtao
AU - Hu, Guojun
AU - Liu, Zi Yuan
AU - Yan, Dongni
AU - Serikuly, Nazar
AU - Alpyshov, Erik T.
AU - Demin, Konstantin A.
AU - Galstyan, David S.
AU - Strekalova, Tatiana
AU - de Abreu, Murilo S.
AU - Amstislavskaya, Tamara G.
AU - Kalueff, Allan V.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Kava kava (Piper methysticum) is a medicinal plant containing kavalactones that exert potent sedative, analgesic and anti-stress action. However, their pharmacological effects and molecular targets remain poorly understood. The zebrafish (Danio rerio) has recently emerged as a powerful new model organism for neuroscience research and drug discovery. Here, we evaluate the effects of acute and chronic exposure to kava and kavalactones on adult zebrafish anxiety, aggression and sociality, as well as on their neurochemical, neuroendocrine and genomic responses. Supporting evolutionarily conserved molecular targets, acute kava and kavalactones evoked dose-dependent behavioral inhibition, upregulated brain expression of early protooncogenes c-fos and c-jun, elevated brain monoamines and lowered whole-body cortisol. Chronic 7-day kava exposure evoked similar behavioral effects, did not alter cortisol levels, and failed to evoke withdrawal-like states upon discontinuation. However, chronic kava upregulated several microglial (iNOS, Egr-2, CD11b), astrocytal (C3, C4B, S100a), epigenetic (ncoa-1) and pro-inflammatory (IL-1β, IL-6, TNFa) biomarker genes, downregulated CD206 and IL-4, and did not affect major apoptotic genes in the brain. Collectively, this study supports robust, evolutionarily conserved behavioral and physiological effects of kava and kavalactones in zebrafish, implicates brain monoamines in their acute effects, and provides novel important insights into potential role of neuroglial and epigenetic mechanisms in long-term kava use.
AB - Kava kava (Piper methysticum) is a medicinal plant containing kavalactones that exert potent sedative, analgesic and anti-stress action. However, their pharmacological effects and molecular targets remain poorly understood. The zebrafish (Danio rerio) has recently emerged as a powerful new model organism for neuroscience research and drug discovery. Here, we evaluate the effects of acute and chronic exposure to kava and kavalactones on adult zebrafish anxiety, aggression and sociality, as well as on their neurochemical, neuroendocrine and genomic responses. Supporting evolutionarily conserved molecular targets, acute kava and kavalactones evoked dose-dependent behavioral inhibition, upregulated brain expression of early protooncogenes c-fos and c-jun, elevated brain monoamines and lowered whole-body cortisol. Chronic 7-day kava exposure evoked similar behavioral effects, did not alter cortisol levels, and failed to evoke withdrawal-like states upon discontinuation. However, chronic kava upregulated several microglial (iNOS, Egr-2, CD11b), astrocytal (C3, C4B, S100a), epigenetic (ncoa-1) and pro-inflammatory (IL-1β, IL-6, TNFa) biomarker genes, downregulated CD206 and IL-4, and did not affect major apoptotic genes in the brain. Collectively, this study supports robust, evolutionarily conserved behavioral and physiological effects of kava and kavalactones in zebrafish, implicates brain monoamines in their acute effects, and provides novel important insights into potential role of neuroglial and epigenetic mechanisms in long-term kava use.
KW - Behavior
KW - Cortisol
KW - Kava
KW - Monoamines
KW - Neuroglia
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85084209463&partnerID=8YFLogxK
U2 - 10.1016/j.ntt.2020.106881
DO - 10.1016/j.ntt.2020.106881
M3 - Article
C2 - 32240749
AN - SCOPUS:85084209463
SN - 0892-0362
VL - 79
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
M1 - 106881
ER -