Behavioral and molecular evidence for psychotropic effects in L-theanine

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.

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.

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.

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).

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.