Extracellular concentration of endogenous free D-serine in the rat brain as revealed by in vivo microdialysis.

Using an in vivo microdialysis technique, we have measured the extracellular concentration of endogenous free D-serine in comparison with that of L-serine, glycine and L-glutamate in the discrete brain areas of the freely moving rat. A high concentration of D-serine was observed in the dialysate obtained from the medial prefrontal cortex and striatum, whereas the cerebellar dialysate contained only a trace amount of the D-amino acid. The regional variation in the basal overflow of D-serine was proportional to that of its tissue levels which has been shown to closely correlate with the distribution of the N-methyl-D-aspartate type excitatory amino acid receptor. In contrast, the extracellular release of glycine and L-glutamate was higher in the cerebellum and very low in the striatum. The extracellular concentrations of L-serine were more than three times those of striatal D-serine in the three regions. Neither addition of a sodium channel blocker, tetrodotoxin (2 microM), nor deprivation of Ca2+ from the perfusate reduced the basal extracellular levels of the four amino acids tested in the medial prefrontal cortex. Furthermore, intra-frontal cortex perfusion of a sodium channel activator, veratrine (200 micrograms/ml), caused an increase in the extracellular release of glycine and L-glutamate but a slight decrease in that of D-serine in a tetrodotoxin-sensitive manner in the cortical region.(ABSTRACT TRUNCATED AT 250 WORDS)