title: Behavioral and molecular evidence for psychotropic effects in L-theanine.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Wakabayashi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Midori
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Shuichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C026166:theanine; D002118:Calcium