Elsevier

Neuroscience

Volume 66, Issue 3, June 1995, Pages 635-643
Neuroscience

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

https://doi.org/10.1016/0306-4522(94)00597-XGet rights and content

Abstract

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 μM), 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 μg/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.

Because d-serine is known to act as a selective agonist for the glycine modulatory site of the N-methyl- d-aspartate receptor, the presence of extracellular d-serine release and its distribution profile in the brain further support the view that d-serine as well as glycine may be endogenous modulators of brain N-methyl- d-aspartate receptors. The tetrodotoxin- and Ca2+-deprivation-resistant nature and the lack of veratrine-induced increase suggest that d-serine might be liberated into the extracellular space from non-neuronal cells or certain exceptional neuronal cells probably by a carrier-mediated process.

Reference (52)

  • LeviG. et al.

    Evidence in favor of a neurotransmitter role of glycine in the rat cerebral cortex

    Brain Res.

    (1982)
  • LeviG. et al.

    Carrier-mediated release of neurotransmitters

    Trends Neurosci.

    (1993)
  • NaasE. et al.

    Glycine receptor immunoreactivity in rat and human cerebral cortex

    Brain Res.

    (1991)
  • NagataY. et al.

    Distribution of free d-serine in vertebrate brains

    Brain Res.

    (1994)
  • PourchoR.G. et al.

    Immunocytochemical evidence for the involvement of glycine in sensory centers of the rat brain

    Neuroscience

    (1992)
  • RennoW.M. et al.

    Systemic morphine reduces GABA release in the lateral but not the medial portion of the midbrain periaqueductal gray of the rat

    Brain Res.

    (1992)
  • ShapiraR. et al.

    Differential racemization of aspartate and serine in human myelin basic protein

    Biochem. biophys. Res. Commun.

    (1987)
  • TakashimaM. et al.

    Modulation of cerebral acetylcholine metabolism by the dorsal diencephalic conduction system in the rat

    Neurochem. Int.

    (1992)
  • TaniiY. et al.

    Phencyclidine increases extracellular dopamine metabolites in rat medial frontal cortex as measured by in vitro dialysis

    Neurosci. Lett.

    (1990)
  • TothE. et al.

    Effect of nicotine on levels of extracellular amino acids in regions of the rat brain in vivo

    Neuropharmacology

    (1993)
  • WesterinkB.H.C. et al.

    Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems

    Life Sci.

    (1987)
  • AjimaA. et al.

    Brain dialysis: detection of acetylcholine release in the striatum, hippocampus and frontal cortex of freely moving rats

    Biogenic Amines

    (1988)
  • BjörklundA. et al.

    Dopamine-containing systems in the CNS

  • ButcherS.P. et al.

    In vivo studies on the extracellular, and veratrine-releasable, pools of endogenous amino acids in the rat striatum: effects of corticostriatal deafferentation and kainic acid lesion

    J. Neurochem.

    (1987)
  • ChouinardM.L. et al.

    Presence of the N-methyl- d-aspartate-associated glycine receptor agonist d-serine, in human temporal cortex: comparison of normal, parkinson and alzheimer tissues

    J. Neurochem.

    (1993)
  • CorriganJ.J.

    d-Amino acids in animals

    Science

    (1969)
  • Cited by (189)

    View all citing articles on Scopus
    View full text