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Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish

Monoamine oxidases (MAO) are a valuable class of mitochondrial enzymes with a critical role in neuromodulation. In this study, we investigated the effect of natural MAO inhibitors on novel environment-induced anxiety by using the zebrafish novel tank test (NTT). Because zebrafish spend more time at...

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Autores principales: Jaka, Oihane, Iturria, Iñaki, van der Toorn, Marco, Hurtado de Mendoza, Jorge, Latino, Diogo A. R. S., Alzualde, Ainhoa, Peitsch, Manuel C., Hoeng, Julia, Koshibu, Kyoko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165606/
https://www.ncbi.nlm.nih.gov/pubmed/34079463
http://dx.doi.org/10.3389/fphar.2021.669370
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author Jaka, Oihane
Iturria, Iñaki
van der Toorn, Marco
Hurtado de Mendoza, Jorge
Latino, Diogo A. R. S.
Alzualde, Ainhoa
Peitsch, Manuel C.
Hoeng, Julia
Koshibu, Kyoko
author_facet Jaka, Oihane
Iturria, Iñaki
van der Toorn, Marco
Hurtado de Mendoza, Jorge
Latino, Diogo A. R. S.
Alzualde, Ainhoa
Peitsch, Manuel C.
Hoeng, Julia
Koshibu, Kyoko
author_sort Jaka, Oihane
collection PubMed
description Monoamine oxidases (MAO) are a valuable class of mitochondrial enzymes with a critical role in neuromodulation. In this study, we investigated the effect of natural MAO inhibitors on novel environment-induced anxiety by using the zebrafish novel tank test (NTT). Because zebrafish spend more time at the bottom of the tank when they are anxious, anxiolytic compounds increase the time zebrafish spend at the top of the tank and vice versa. Using this paradigm, we found that harmane, norharmane, and 1,2,3,4-tetrahydroisoquinoline (TIQ) induce anxiolytic-like effects in zebrafish, causing them to spend more time at the top of the test tank and less time at the bottom. 2,3,6-trimethyl-1,4-naphtoquinone (TMN) induced an interesting mix of both anxiolytic- and anxiogenic-like effects during the first and second halves of the test, respectively. TIQ was unique in having no observable effect on general movement. Similarly, a reference MAO inhibitor clorgyline—but not pargyline—increased the time spent at the top in a concentration-dependent manner. We also demonstrated that the brain bioavailability of these compounds are high based on the ex vivo bioavailability assay and in silico prediction models, which support the notion that the observed effects on anxiety-like behavior in zebrafish were most likely due to the direct effect of these compounds in the brain. This study is the first investigation to demonstrate the anxiolytic-like effects of MAO inhibitors on novel environment-induced anxiety in zebrafish.
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spelling pubmed-81656062021-06-01 Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish Jaka, Oihane Iturria, Iñaki van der Toorn, Marco Hurtado de Mendoza, Jorge Latino, Diogo A. R. S. Alzualde, Ainhoa Peitsch, Manuel C. Hoeng, Julia Koshibu, Kyoko Front Pharmacol Pharmacology Monoamine oxidases (MAO) are a valuable class of mitochondrial enzymes with a critical role in neuromodulation. In this study, we investigated the effect of natural MAO inhibitors on novel environment-induced anxiety by using the zebrafish novel tank test (NTT). Because zebrafish spend more time at the bottom of the tank when they are anxious, anxiolytic compounds increase the time zebrafish spend at the top of the tank and vice versa. Using this paradigm, we found that harmane, norharmane, and 1,2,3,4-tetrahydroisoquinoline (TIQ) induce anxiolytic-like effects in zebrafish, causing them to spend more time at the top of the test tank and less time at the bottom. 2,3,6-trimethyl-1,4-naphtoquinone (TMN) induced an interesting mix of both anxiolytic- and anxiogenic-like effects during the first and second halves of the test, respectively. TIQ was unique in having no observable effect on general movement. Similarly, a reference MAO inhibitor clorgyline—but not pargyline—increased the time spent at the top in a concentration-dependent manner. We also demonstrated that the brain bioavailability of these compounds are high based on the ex vivo bioavailability assay and in silico prediction models, which support the notion that the observed effects on anxiety-like behavior in zebrafish were most likely due to the direct effect of these compounds in the brain. This study is the first investigation to demonstrate the anxiolytic-like effects of MAO inhibitors on novel environment-induced anxiety in zebrafish. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8165606/ /pubmed/34079463 http://dx.doi.org/10.3389/fphar.2021.669370 Text en Copyright © 2021 Jaka, Iturria, van der Toorn, Hurtado de Mendoza, Latino, Alzualde, Peitsch, Hoeng and Koshibu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Jaka, Oihane
Iturria, Iñaki
van der Toorn, Marco
Hurtado de Mendoza, Jorge
Latino, Diogo A. R. S.
Alzualde, Ainhoa
Peitsch, Manuel C.
Hoeng, Julia
Koshibu, Kyoko
Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title_full Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title_fullStr Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title_full_unstemmed Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title_short Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
title_sort effects of natural monoamine oxidase inhibitors on anxiety-like behavior in zebrafish
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165606/
https://www.ncbi.nlm.nih.gov/pubmed/34079463
http://dx.doi.org/10.3389/fphar.2021.669370
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