Behavioral and molecular evidence for psychotropic effects in L-theanine

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 noncompetitive 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.