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

Psychopharmacology (Berl). 2018 Jan;235(1):37-45. doi: 10.1007/s00213-017-4743-1. Epub 2017 Oct 3.


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.

Methods: 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.

Results: 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).

Conclusions: 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.

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

MeSH terms

  • Amino Acids / cerebrospinal fluid*
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety / diagnostic imaging
  • Anxiety / psychology*
  • Behavior, Animal / drug effects
  • Chromatography, High Pressure Liquid
  • Depression / diagnostic imaging
  • Depression / metabolism
  • Depression / psychology
  • Fluorodeoxyglucose F18
  • Glutamates / pharmacology*
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects*
  • Magnetic Resonance Imaging
  • Male
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Rats
  • Rats, Inbred WKY


  • Amino Acids
  • Anti-Anxiety Agents
  • Glutamates
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • theanine