Study for interaction between D-serine synthesis and development of morphine tolerance

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Repeated administration of morphine for 30 days produced a significant augmentations of both the mRNA and protein expressions of serine racemase in all the brain regions, and caused a slight but significant elevation in the elevated D-seirne revel in the cortex, striatum and hippocampus. The antinociception induced by the intracerebroventricular (i.c.v.) administration of D-serine was attenuated by i.c.v. administration of midazolam. These results indicate the elevated D-serine level following the chronic morphine treatment could at least in part be involved in the activation of NMDA receptors via the glycine site.