L-theanine ameliorate depressive-like behavior in a chronic unpredictable mild stress rat model via modulating the monoamine levels in limbic-cortical-striatal-pallidal-thalamic-circuit related brain regions. Shen Manjun,Yang Yi,Wu Ying,Zhang Beibei,Wu Haishan,Wang Lu,Tang Hui,Chen Jindong Phytotherapy research : PTR L-theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety-like and antidepressant-like properties. This study aims to investigate the effects of L-theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l-theanine on the symptoms of depression was examined through the open-field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5-HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic-cortical-striatal-pallidal-thalamic (LCSPT)-circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L-theanine ameliorated the depressive-like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L-theanine administration significantly increased the levels of 5-HT, NE, and DA. In the ST, the levels of 5-HT and DA were increased after the administration of L-theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L-theanine. Taken together, these results indicated that L-theanine has possibly antidepressant-like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT-circuit related brain regions. 10.1002/ptr.6237