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

Neuroscience. 1995 Jun;66(3):635-43. doi: 10.1016/0306-4522(94)00597-x.


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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cerebellum / metabolism
  • Corpus Striatum / metabolism
  • Extracellular Space / chemistry
  • Extracellular Space / metabolism
  • Glutamic Acid / metabolism
  • Glycine / metabolism
  • Kinetics
  • Male
  • Microdialysis / methods
  • Organ Specificity
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Serine / analysis
  • Serine / metabolism*
  • Sodium Channel Blockers
  • Stereoisomerism
  • Tetrodotoxin / pharmacology
  • Veratrine / pharmacology


  • Amino Acids
  • Sodium Channel Blockers
  • Glutamic Acid
  • Tetrodotoxin
  • Serine
  • Veratrine
  • Glycine