Major depression is a common disorder, with a life time prevalence of about 15 %, perhaps as high as 50 % when bipolar and chronic minor depression were included. While most depressive symptoms are eliminated by the current pharmacological treatments, as many as 50-60% of patients have incomplete recovery or significant side effects. Current antidepressant pharmacological treatments are hypothesized act through monoamine receptor hypothesis. However, in addition to monoamine receptor hypothesis, another hypothesis for the pathophysiology of depression implicated to the N-methyl-D-aspartate(NMDA) receptor which may providing additional benefits for resistant to the current antidepressant. In our preliminary study, we found sarcosine (glycine transporter-1 inhibitor) 560 mg/kg exerts antidepressant-like effect in rats. Nevertheless, until now, no studies focus on the dose-dependent and sustained effect of sarcosine. Additionally, the implication morphological, and molecular level of brain regions related with mood modulation and such neo-antidepressant have not yet been well explored. In order to elucidate and test the action of NMDA receptor on the pathogenesis of depression, we conducted this study to investigate the impact sarcosine after administrating different dosage in the Porsolt swim test, a behavioral model of depression. Additional biochemical and behavioral experiments were undertaken to determine whether the antidepressant-like properties of sarcosine involve α-amino-3- hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor throughput. Finally, we hope our finding can improve the efficacy of anti-depression treatment.
