Psychopharmacology

, Volume 219, Issue 4, pp 1099–1109 | Cite as

Behavioral and molecular evidence for psychotropic effects in l-theanine

  • Chisato Wakabayashi
  • Tadahiro Numakawa
  • Midori Ninomiya
  • Shuichi Chiba
  • Hiroshi Kunugi
Original Investigation

Abstract

Rationale

l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea and historically considered to be a relaxing agent. It is a glutamate derivative and has an affinity for glutamatergic receptors. However, its psychotropic effects remain unclear.

Objectives

To elucidate effects of l-theanine on psychiatric disease-related behaviors in mice and its molecular basis focusing on brain-derived neurotrophic factor (BDNF) and N-methyl-d-aspartate (NMDA) receptor.

Methods

We examined the effects of l-theanine on behaviors in mice by using the open-field test (OFT), forced swim test (FST), elevated plus-maze test (EPMT), and prepulse inhibition (PPI) of acoustic startle. By western blot analysis, we looked at the effect of l-theanine on the expression of BDNF and related proteins in the hippocampus and cerebral cortex. To determine whether l-theanine has agonistic action on the NMDA receptor, we performed Fluo-3 intracellular Ca2+ imaging in cultured cortical neurons.

Results

Single administration of l-theanine significantly attenuated MK-801-induced deficits in PPI. Subchronic administration (3-week duration) of l-theanine significantly reduced immobility time in the FST and improved baseline PPI. Western blotting analysis showed increased expression of BDNF protein in the hippocampus after subchronic administration of l-theanine. In cultured cortical neurons, l-theanine significantly increased the intracellular Ca2+ concentration, and this increase was suppressed by competitive and non-competitive NMDA receptor antagonists (AP-5 and MK-801, respectively).

Conclusions

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.

Keywords

l-theanine MK-801 (dizocilpine) N-methyl d-aspartate (NMDA) receptor Schizophrenia Prepulse inhibition Brain-derived neurotrophic factor (BDNF) Behavior Glutamate Antidepressant 

Abbreviations

OFT

Open-field test

PPI

Prepulse inhibition

FST

Forced swim test

EPMT

Elevated plus-maze test

NMDA

N-methyl-d-aspartate

GABA

Gamma-aminobutyric acid

AMPA

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BDNF

Brain-derived neurotrophic factor

PCP

Phencyclidine

AP-5

d-(−)-2-amino-5-phosphonopentanoic acid

Supplementary material

213_2011_2440_MOESM1_ESM.doc (178 kb)
ESM 1(DOC 178 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Chisato Wakabayashi
    • 1
  • Tadahiro Numakawa
    • 1
    • 2
  • Midori Ninomiya
    • 1
  • Shuichi Chiba
    • 1
  • Hiroshi Kunugi
    • 1
    • 2
  1. 1.Department of Mental Disorder ResearchNational Institute of Neuroscience, National Center of Neurology and PsychiatryTokyoJapan
  2. 2.Core Research for Evolutional Science and Technology Program (CREST)Japan Science and Technology Agency (JST)TokyoJapan

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