@article{ee101b5fbd9945e6b0d6fa9fad36d356,
title = "Behavioral and physiological effects of acute and chronic kava exposure in adult zebrafish",
abstract = "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-1 beta, IL-6, TNF alpha) 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.",
keywords = "behavior, cortex, cortisol, extract, kava, microglia, model, monoamines, neuroglia, responses, stress, symptoms, withdrawal, zebrafish, Kava, Neuroglia, Cortisol, Monoamines, MICROGLIA, Behavior, STRESS, EXTRACT, Zebrafish, SYMPTOMS, MODEL, RESPONSES, CORTEX, WITHDRAWAL",
author = "D.M. Wang and L.E. Yang and J.T. Wang and G.J. Hu and Z.Y. Liu and D.N. Yan and N. Serikuly and E.T. Alpyshov and K.A. Demin and D.S. Galstyan and T. Strekalova and {de Abreu}, M.S. and T.G. Amstislavskaya and A.V. Kalueff",
note = "Funding Information: This study was supported by the Zebrafish Platform Construction funds from the School of Pharmacy of the Southwest University (Chongqing, China). AVK is the President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) and the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) that coordinated this collaborative project. KAD is supported by the Russian Foundation for Basic Research grant 18?34?00996, the President of Russia's Graduate Fellowship and the SPSU Rector's Productivity Fellowship for PhD students. The collaboration was also supported by the Russian Science Foundation (RSF) grants 19?15?00053 and 20-65-46006. TGA is supported by the budgetary funding for basic research (project AAAA-A16-116021010228-0) from the Scientific Research Institute of Physiology and Basic Medicine (Novosibirsk, Russia). The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish. The authors acknowledge Andrey D. Volgin for his efforts protecting Siberia, and Konstantin N. Zabegalov and Tatyana O. Kolesnikova for their assitance with neurochemical analyses in the present study. We also sincerely thank Professor Raul R. Gainetdivov, Dr. Evgeniya V. Efimova and Mr. Mikael S. Mor (Institute of Translational Biomedicine, St. Petersburg State Universitity, St. Petersburg, Russia) for their generous assistance with neurochemical analyses in the present study. Funding Information: This study was supported by the Zebrafish Platform Construction funds from the School of Pharmacy of the Southwest University (Chongqing, China). AVK is the President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com ) and the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) that coordinated this collaborative project. KAD is supported by the Russian Foundation for Basic Research grant 18‐34‐00996 , the President of Russia's Graduate Fellowship and the SPSU Rector's Productivity Fellowship for PhD students. The collaboration was also supported by the Russian Science Foundation (RSF) grants 19‐15‐00053 and 20-65-46006 . TGA is supported by the budgetary funding for basic research (project AAAA-A16-116021010228-0) from the Scientific Research Institute of Physiology and Basic Medicine (Novosibirsk, Russia). The funders had no role in the design, analyses and interpretation of the submitted study, or decision to publish. The authors acknowledge Andrey D. Volgin for his efforts protecting Siberia, and Konstantin N. Zabegalov and Tatyana O. Kolesnikova for their assitance with neurochemical analyses in the present study. We also sincerely thank Professor Raul R. Gainetdivov, Dr. Evgeniya V. Efimova and Mr. Mikael S. Mor (Institute of Translational Biomedicine, St. Petersburg State Universitity, St. Petersburg, Russia) for their generous assistance with neurochemical analyses in the present study. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = may,
day = "1",
doi = "10.1016/j.ntt.2020.106881",
language = "English",
volume = "79",
journal = "Neurotoxicology and Teratology",
issn = "0892-0362",
publisher = "Elsevier Inc.",
}