L-Theanine Ameliorates Chronic Unpredictable Mild Stress-Induced Depressive Behavior Through Differential Modulation of Hippocampus and Prefrontal Cortex

Abstract

Aim: This study was designed to determine the antidepressant-like effect of L-theanine in mice exposed to chronic unpredictable mild stress (CUMS). Methods: In the present study CUMS procedure of 3 weeks (21 days) was used for the induction of depression related behavior. On day 22nd, behavioral testing was performed using an actophotometer for locomotor activity. On day 23rd, depression-related behavior was assessed using tail suspension test (TST) and the forced swim test (FST). Following behavioral studies, mice were sacrificed, and the PFC and hippocampus were dissected for the neurochemical assays of serotonin, glutamate, and nitrite. Results: It was observed that the daily treatment with L-Theanine (5 and 10 mg/kg/day i.p.) did not affect the activity count of the mice but ameliorated the effect of CUMS in TST (P<0.01, P<0.01) and FST. Also, the daily treatment with L-Theanine (2.5, 5, and 10 mg/kg/day i.p.) in the CUMS exposed mice significantly increased the PFC serotonin level (P < 0.001, P < 0.001, P < 0.001) without affecting the hippocampal serotonin level. However, the daily treatment of L-Theanine (2.5, 5, and 10 mg/kg/day i.p.) in mice exposed to CUMS significantly decreased the glutamate level (P<0.001) and increased the nitrite level (P<0.001, P<0.001, P<0.001) in hippocampal region while the the daily treatment of L-Theanine (2.5, 5, and 10 mg/kg/day i.p.) in mice exposed to CUMS significantly increased the glutamate level (P < 0.001, P < 0.001, P < 0.001) and nitrite level (P<0.001, P<0.001, P<0.001) region of the mice as compared to its respective control. Conclusion: In conclusion, LT exerted an antidepressant-like effect in mice exposed to CUMS by increasing serotonin, glutamate, and nitrite in the PFC and decreasing glutamate in the hippocampus..