AMPA Receptor–mTOR Activation is Required for the Antidepressant-Like Effects of Sarcosine during the Forced Swim Test in Rats: Insertion of AMPA Receptor may Play a Role

摘要: Sarcosine, an endogenous amino acid, is a competitive inhibitor of the type I glycine transporter and N-methyl-D-aspartate receptor (NMDAR) coagonist. Recently, we found that sarcosine, NMDAR enhancer, can improve depression-related behaviors in rodents humans. This result differs from previous studies, which have reported antidepressant effects antagonists. The mechanisms underlying therapeutic response sarcosine remain unknown. study examines role mammalian target rapamycin (mTOR) signaling α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPAR) activation, are involved antidepressant-like several glutamatergic system modulators. forced swim test (FST) expression levels phosphorylated mTOR proteins were examined absence or presence AMPAR inhibitors. In addition, influence on trafficking was determined by analyzing phosphorylation subunit GluR1 at PKA site (often considered indicator for membrane insertion neurons). A single injection exhibited rats FST rapidly activated pathway, significantly blocked 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) pretreatment. Moreover, NBQX pretreatment eliminated ability to stimulate proteins. Furthermore, its increased after acute vivo treatment. results demonstrated exerts enhancing AMPAR–mTOR pathway activity facilitating insertion. Highlights: - exerted with concomitant increase activation