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Effect of Theanine, r-Glutamylethylamide, on Brain Monoamines and Striatal Dopamine Release in Conscious Rats
Abstract
Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.
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l-theanine crosses the blood-brain barrier via a leucine-preferred transport system and affects the central nervous system through several pathways, thereby exerting antidepressant and mood-enhancing effects.
“l-theanine crosses the blood–brain barrier via a leucine-preferred transport system and affects the central nervous system through several pathways, thereby exerting antidepressant and mood-enhancing effects [31,32,33].”
Modulation of the monoamine and glutamic acid and glycine systems may also contribute to the four weeks psychotropic effects of L-theanine.
“The modulation of the monoamine [14,15,16,17] and glutamic acid and glycine [18,19] systems may also contribute to these four weeks psychotropic effects.”
From Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial (2019) · cites this paper as [16]
Animal studies have demonstrated that L-theanine can dose-dependently increase levels of dopamine in the rat striatum.
“Animal studies have demonstrated that it can dose-dependently increase levels of dopamine in the rat striatum”
From A Double-Blind, Placebo-Controlled Study Evaluating the Effects of Caffeine and L-Theanine Both Alone and in Combination on Cerebral Blood Flow, Cognition and Mood (2015) · cites this paper as Yokogoshi et al. 1998
Animal studies have revealed that L-theanine affected dopamine and serotonin concentrations in the brain, underlying its anxiolytic effect.
“Animal studies have revealed that L-theanine affected dopamine and serotonin concentrations in the brain, underlying its anxiolytic effect [1,2].”
From Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses (2012) · cites this paper as [1]
In rats, L-theanine was detected in neural tissue after intragastric administration and was transported via a leucine-preferring transport system.
“Also in rats, two separate studies from the same research group [60,67], detected the presence of L-theanine in neural tissue after its intragastric administration, and that this transport occurred via a leucinepreferring transport system.”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [60]
Yokogoshi et al found higher serotonin levels in rat striatum, hippocampus, and hypothalamus after intragastric L-theanine compared with saline-treated controls.
“Prior to that, Yokogoshi and colleagues had found significantly higher levels of dopamine in rat striatum after intragastric administration of L-theanine, alongside higher levels of serotonin in striatum, hippocampus and hypothalamus, as compared to the saline-treated controls [60].”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [60]
Yokogoshi et al found significantly higher dopamine levels in rat striatum after intragastric L-theanine compared with saline-treated controls.
“Prior to that, Yokogoshi and colleagues had found significantly higher levels of dopamine in rat striatum after intragastric administration of L-theanine, alongside higher levels of serotonin in striatum, hippocampus and hypothalamus, as compared to the saline-treated controls [60].”
From Psychotropic effects of L-theanine and its clinical properties: from the management of anxiety and stress to a potential use in schizophrenia (2019) · cites this paper as [60]
L-THE consumed orally as a component of mango sorbet (200 mg) is a lower dose compared to rat studies (1500 mg/day and 2000 mg/kg intraperitoneal).
“Further, L-THE consumed orally as a component of mango sorbet (200 mg) is a lower dose compared to the pharmacodynamic rat studies by Yokogoshi et al. [45] as well as Yokogoshi and Kobayashi [46], which were both similar in design (1500 mg/day and 2000 mg/kg of L-THE administered intraperitoneally).”
A dose-dependent hypotensive effect occurred in spontaneously hypertensive rats injected with L-theanine in vivo.
“A dose-dependent hypotensive effect was occurred in spontaneously hypertensive rats injected with L-theanine in vivo [31]”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [31]
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Metadata
- Authors
- Yokogoshi, H., Kobayashi, M., Mochizuki, M., & Terashima, T.
- Affiliations
- Shizuoka University (JP)
- Corresponding author
- Yokogoshi, Hidehiko
- ORCID
- Kobayashi, Miki
- Venue
- Neurochemical Research
- Published
- 1998-05
- Volume
- 23
- Issue
- 5
- Pages
- 667-673
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W1602115450
- Cited by
- 229
- References
- 28
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 17 · 2023: 5 · 2022: 14 · 2021: 5 · 2020: 10 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 10 · 2015: 11 · 2014: 8 · 2013: 13 · 2012: 9
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- theanine, striatal dopamine release, brain monoamines, serotonin, norepinephrine, DOPAC, 5-hydroxyindoleacetic acid, brain amino acids, blood-brain barrier, AP5, MK-801, neurotransmitter metabolism
- MeSH terms
- Alanine, Amino Acids, Animals, Brain, Carrier Proteins, Consciousness, Corpus Striatum, Dopamine, Glutamates, Hydroxyindoleacetic Acid, Kinetics, Leucine, Male, Norepinephrine, Organ Specificity, Stereoisomerism, Tea, 3,4-Dihydroxyphenylacetic Acid, Biogenic Monoamines, 2-Amino-5-phosphonovalerate, Dizocilpine Maleate, Rats, Wistar, Rats
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