, Volume 235, Issue 1, pp 37–45 | Cite as

Effects of l-theanine on anxiety-like behavior, cerebrospinal fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats

  • Shintaro Ogawa
  • Miho Ota
  • Jun Ogura
  • Koichi Kato
  • Hiroshi KunugiEmail author
Original Investigation


Rationale and objectives

The amino acid l-theanine (N-ethyl-l-glutamine) has historically been considered a relaxing agent. In the present study, we examined the effects of repeated l-theanine administration on behavior, levels of amino acids in the cerebrospinal fluid (CSF), and hippocampal activity in Wistar Kyoto (WKY) rats, an animal model of anxiety and depressive disorders.


Behavioral tests were performed after 7–10 days of l-theanine (0.4 mg kg−1 day−1) or saline administration, followed by CSF sampling for high-performance liquid chromatography (HPLC) analysis. An independent set of animals was subjected to [18F]fluorodeoxyglucose positron emission tomography (PET) scanning after the same dose of l-theanine or saline administration for 7 days.


In the elevated plus maze test, the time spent in the open arms was significantly longer in the l-theanine group than in the saline group (P = 0.035). In addition, significantly lower CSF glutamate (P = 0.039) and higher methionine (P = 0.024) concentrations were observed in the l-theanine group than in the saline group. A significant increase in the standard uptake value ratio was observed in the hippocampus/cerebellum of the l-theanine group (P < 0.001).


These results suggest that l-theanine enhances hippocampal activity and exerts anxiolytic effects, which may be mediated by changes in glutamate and methionine levels in the brain. Further study is required to more fully elucidate the mechanisms underlying the effects of l-theanine.


Amino acids Cerebrospinal fluid [18F]Fluorodeoxyglucose l-Theanine (N-ethyl-L-glutamine) Positron emission tomography Wistar Kyoto rats 



The authors would like to thank Mr. Makoto Funasaka for his expert technical assistance with the PET experiments and Ms. Midori Ninomiya for her instructions on rat CSF collection.

Compliance with ethical standards

Conflict of interest

This research study was funded by an unrestricted research grant provided by Taiyo Life Insurance Himawari Foundation, Tokyo, Japan. This funding agency had no role in the design, methods, analysis, or preparation of the paper.

Supplementary material

213_2017_4743_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 26.4 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Shintaro Ogawa
    • 1
  • Miho Ota
    • 1
  • Jun Ogura
    • 1
  • Koichi Kato
    • 2
    • 3
  • Hiroshi Kunugi
    • 1
    Email author
  1. 1.Department of Mental Disorder Research, National Institute of NeuroscienceNational Center of Neurology and PsychiatryTokyoJapan
  2. 2.Department of Advanced Neuroimaging, Integrative Brain Imaging CenterNational Center of Neurology and PsychiatryTokyoJapan
  3. 3.Department of Functional Brain Research, National Institute of NeuroscienceNational Center of Neurology and PsychiatryTokyoJapan

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