Effect of systemic administration of D-serine on the levels of D- and L-serine in several brain areas and periphery of rat.

To obtain further insight into the distribution and metabolism of exogenous D-serine, we have investigated the effect of the intraperitoneal administration of D-serine (10 mmol/kg) on the concentrations of D- and L-serine in several brain areas and periphery of infant and adult rats. The administration produced a significant augmentation of the D-serine levels not only in the cortex but also in the hippocampus, striatum, cerebellum and periphery. The rapid decline in the enhanced D-serine levels was observed in the periphery and cerebellum, whereas the injection caused a prolonged elevation of the D-serine levels in the cortex and hippocampus. The application caused a slight increase in the L-serine levels in several brain areas and periphery 3 or 6 h after the injection, whereas a significant decrease in the L-serine concentration was observed in the periphery, diencephalon and cerebellum 3 or 7 days after the injection. Because a structural abnormality and N-methyl-D-aspartate (NMDA) receptor hypofunction has been demonstrated in the cortex and hippocampus of schizophrenic subjects, D-serine treatment may offer a new therapeutic approach to diseases related to the hypofunction of NMDA receptors such as schizophrenia.