Behavioral and molecular evidence for psychotropic effects in l-theanine

Wakabayashi, Chisato; Numakawa, Tadahiro; Ninomiya, Midori; Chiba, Shuichi; Kunugi, Hiroshi

doi:10.1007/s00213-011-2440-z

Cited by 58 publications

(53 citation statements)

References 60 publications

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“…In contrast to the results reported here, a previous reported found that L-theanine (4, 20 or 100 mg/kg) had no effect on elevated plus maze behavior in C57BL/J mice when administered acutely or three times daily every other day for three weeks (Wakabayashi et al, 2012). Similarly, 10 mg/kg L-theanine (Heese et al, 2009) had no effect on elevated plus maze behavior in rats, but augmented the anxiolytic-like effects of midazolam (1.5 mg/kg), as well as decreased fine and basic motor movements in this assay (Heese et al, 2009).…”

Section: Discussioncontrasting

confidence: 99%

“…Similarly, 10 mg/kg L-theanine (Heese et al, 2009) had no effect on elevated plus maze behavior in rats, but augmented the anxiolytic-like effects of midazolam (1.5 mg/kg), as well as decreased fine and basic motor movements in this assay (Heese et al, 2009). Other studies suggest that L-theanine produces antidepressant-like behavior in mice (Wakabayashi et al, 2012; Yin et al, 2011) and that when administered to newborn rats L-theanine improves performance in the object recognition memory test (Takeda et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, studies indicate that L-theanine increases BDNF levels (Miodownik et al, 2011; Takeda et al, 2011; Wakabayashi et al, 2012) and L-theanine has also been show to have antagonistic effects on N-methyl d-asparate (NMDA) receptors (Kakuda et al, 2002). Thus, the observations that BDNF levels can be mediated by glutamate actions at NMDA receptors (Castren et al, 1993; Mattson, 2008; Wakabayashi et al, 2012; Zafra et al, 1991) suggest that the antagonistic properties of L-theanine on NMDA receptors may contribute to L-theanine’s behavioral effects. Glutamate is released during opioid withdrawal (i.e., Noda and Nabeshima, 2004) and, thus, L-theanine’s antagonistic effects on NMDA receptors (Kakuda et al, 2002) may account for its ability to reduce opioid withdrawal signs in morphine-dependent rhesus monkeys.…”

Section: Discussionmentioning

confidence: 99%

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l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice

Wise

Premaratne

Gamage

et al. 2012

Pharmacology Biochemistry and Behavior

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L-theanine, 2-Amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that L-theanine has been shown to inhibit caffeine’s stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that L-theanine may suppress opioid withdrawal signs. Additionally, L-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether L-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether L-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. L-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5 h. L-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that L-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice

Wise

Premaratne

Gamage

et al. 2012

Pharmacology Biochemistry and Behavior

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“…We also found that subchronic treatment with L-theanine elevated the swimming time and reduced the immobilization time in the FST. It has been already shown in Wakabayashi et al [45] that L-theanine restores the activity in FST.…”

Section: -Nitropropionic Acid (3-np)mentioning

confidence: 84%

Neuroprotective activity ofL-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum

Sumathi

Asha

Suganya

et al. 2014

International Journal of Neuroscience

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The present study has been designed to investigate the protective effect of L-theanine against 3-nitropropionic acid (3-NP)-induced Huntington's disease (HD)-like symptoms in rats. The present experimental protocol design includes systemic 3-NP acid (10 mg/kg intraperitonially) treatment for 14 d. L-theanine (100 and 200 mg/kg) was given orally, once a day, 1 h before 3-NP acid treatment for 14 d. Body weight and behavioral parameters (Morris water maze, open field test (OFT), forced swim test (FST) and rotarod activity) were assessed on 1st, 5th, 10th and 15th day post-3-NP acid administration. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and mitochondrial enzyme complex. Succinate dehydrogenase (SDH) were measured on the 15th day in the striatum. Systemic 3-NP acid treatment significantly reduced body weight, locomotor activity and oxidative defense. The mitochondrial enzyme activity was also significantly impaired in the striatum region in 3-NP acid-treated animals. L-theanine (100 and 200 mg/kg b.wt.) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-NP acid-treated group. The results of the present study suggest that pretreatment with L-theanine significantly attenuated 3-NP induced oxidative stress and restored the decreased SOD, GSH, CAT and SDH activity. It also decreased the neuronal damage as evidenced by histopathological analysis of striatum. Based on the above study, it has been proved that L-theanine has neuroprotective activity against 3-NP induced neurotoxicity.

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“…14 This led the authors to suggest that the action of theanine may be mediated by the enhancement of calcium utilization via the NMDA receptor. Further support for this proposal has been recently provided by Wakabayashi et al, 15 who inter alia, found that L-theanine administration resulted in an increase in calcium release within cultured cortical neurons. The increase in calcium release was suppressed by both NMDA antagonists AP-5 and MIC-801.…”

Section: Effect On Brain Chemistry and Neurotransmissionmentioning

confidence: 74%

Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders

Lardner

2013

Nutritional Neuroscience

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Theanine (n-ethylglutamic acid), a non-proteinaceous amino acid component of green and black teas, has received growing attention in recent years due to its reported effects on the central nervous system. It readily crosses the blood-brain barrier where it exerts a variety of neurophysiological and pharmacological effects. Its most well-documented effect has been its apparent anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of serotonin and dopamine in selected areas. It has also recently been shown to increase levels of brain-derived neurotrophic factor. An increasing number of studies demonstrate a neuroprotective effects following cerebral infarct and injury, although the exact molecular mechanisms remain to be fully elucidated. Theanine also elicits improvements in cognitive function including learning and memory, in human and animal studies, possibly via a decrease in NMDA-dependent CA1 long-term potentiation (LTP) and increase in NMDA-independent CA1-LTP. Furthermore, theanine administration elicits selective changes in alpha brain wave activity with concomitant increases in selective attention during the execution of mental tasks. Emerging studies also demonstrate a promising role for theanine in augmentation therapy for schizophrenia, while animal models of depression report positive improvements following theanine administration. A handful of studies are beginning to examine a putative role in attention deficit hyperactivity disorder, and theoretical extrapolations to a therapeutic role for theanine in other psychiatric disorders such as anxiety disorders, panic disorder, obsessive compulsive disorder (OCD), and bipolar disorder are discussed.

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Behavioral and molecular evidence for psychotropic effects in l-theanine

Abstract: Our results suggest that L: -theanine has antipsychotic-like and possibly antidepressant-like effects. It exerts these effects, at least in part, through induction of BDNF in the hippocampus and the agonistic action of L: -theanine on the NMDA receptor.

Cited by 58 publications

References 60 publications

l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice

l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice

Neuroprotective activity ofL-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum

Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders

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