Behavioral and molecular evidence for psychotropic effects in l-theanine

• Published in: Psychopharmacologia 2012-02, Vol.219 (4), p.1099-1109
• Main Authors: Wakabayashi, Chisato, Numakawa, Tadahiro, Ninomiya, Midori, Chiba, Shuichi, Kunugi, Hiroshi
• Format: Article
• Language: English
• Subjects: Acoustic startle response; Adult and adolescent clinical studies; Amino acids; Animals; Antagonists; Antidepressants; Behavior, Animal - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Calcium (intracellular); Calcium - metabolism; Calcium imaging; Cortex; Dizocilpine Maleate - pharmacology; Drug therapy; Fluo-3; Gene Expression Regulation - drug effects; Glutamate; Glutamates - administration & dosage; Glutamates - pharmacology; Glutamic acid; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Green tea; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; L-Theanine; Male; Maze Learning - drug effects; Medical sciences; Mice; Mice, Inbred C57BL; MK-801; N-Methyl-D-aspartic acid receptors; Neuroimaging; Neuroleptics; Neurons; Neuropharmacology; Neurosciences; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Proteins; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychotropic drugs; Receptors, N-Methyl-D-Aspartate - agonists; Reflex, Startle - drug effects; Schizophrenia; Western blotting
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2440-z

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 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.