Abstract

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.

Highlights

  • Plants have been a rich source of nutrients and chemical ingredients that help maintain physical and mental health for centuries (Perry and Perry, 2018)

  • To support the validity of our behavioral findings, we demonstrated that these natural Monoamine oxidases (MAO) inhibitors reach the brain by using the ex vivo bioavailability assay and in silico blood brain barrier models

  • The anxiolytic-like effect of harmane is in agreement with previous reports indicating reduction in anxietyrelated behaviors in, for example, elevated plus maze in rodents (Aricioglu and Altunbas, 2003; Khan et al, 2017a)

Read more

Summary

Introduction

Plants have been a rich source of nutrients and chemical ingredients that help maintain physical and mental health for centuries (Perry and Perry, 2018). Scientific interests in these natural sources of health benefits have been steadily rising, where, for example, investigations on “herbal medicine” alone sored from approximately 2,000 publications in 2010 to almost 5,000 publications in 2020 reported on PubMed (accessed Feb 15, 2021). The enzyme catalyzes the oxidative deamination of a variety of monoamines, both endogenous and exogenous It has major roles in metabolizing neurotransmitters, including serotonin, histamine, dopamine, noradrenaline, and adrenaline, and in detoxifying a large variety of endogenous and exogenous amines (Dos Santos Passos et al, 2014; Finberg and Rabey, 2016; Edmondson and Binda, 2018)

Objectives
Methods
Findings
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call