Therapeutic potential and underlying mechanism of sarcosine (N-methylglycine) in N-methyl-D-aspartate (NMDA) receptor hypofunction models of schizophrenia
Journal
Journal of Psychopharmacology
Date Issued
2019
Author(s)
Pei, J.-C.
Hung, W.-L.
Lin, B.-X.
Shih, M.-H.
Lu, L.-Y.
Luo, D.-Z.
Tai, H.-C.
Studer, V.
Min, M.-Y.
Lai, W.-S.
Abstract
BACKGROUND: Compelling animal and clinical studies support the N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia and suggest promising pharmacological agents to ameliorate negative and cognitive symptoms of schizophrenia, including sarcosine, a glycine transporter-1 inhibitor. AIMS AND METHODS: ) mice) NMDAR hypofunction models. RESULTS: mouse models. In Experiment 5, the injection of sarcosine enhanced CSF levels of glycine and serine in rat brain. In Experiments 6-7, we show for the first time that sarcosine facilitated NMDAR-mediated hippocampal field excitatory postsynaptic potentials and influenced the movement of surface NMDARs at extrasynaptic sites. CONCLUSIONS: Sarcosine effectively regulated the surface trafficking of NMDARs, NMDAR-evoked electrophysiological activity, brain glycine levels and MK-801-induced abnormalities in the brain, which contributed to the amelioration of behavioral deficits in mouse models of NMDAR hypofunction.
SDGs
Type
journal article