期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 16, 期 6, 页码 1395-1406出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1461145712001484
关键词
AMPA receptor; D-serine; in vivo dialysis; medial prefrontal cortex
资金
- CREST (Core Research for Evolutional Science Technology)
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [24390280] Funding Source: KAKEN
In mammalian brains, D-serine has been shown to be required for the regulation of glutamate neurotransmission as an endogenous co-agonist for the N-methyl-D-aspartate type glutamate receptor that is essential for the expression of higher-order brain functions. The exact control mechanisms for the extracellular D-serine dynamics, however, await further elucidation. To obtain an insight into this issue, we have characterized the effects of agents acting at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPA) type glutamate receptor on the extracellular D-serine contents in the medial prefrontal cortex of freely moving rats by an in vivo microdialysis technique in combination with high-performance liquid chromatography with fluorometric detection. In vivo experiments are needed in terms of a crucial role of D-serine in the neuron-glia communications despite the previous in vitro studies on AMPA receptor-D-serine interactions using the separated preparations of neurons or glial cells. Here, we show that the intra-cortical infusion of (S)-AMPA, an active enantiomer at the AMPA receptor, causes a significant and concentration-dependent reduction in the prefrontal extracellular contents of D-serine, which is reversed by an AMPA/kainate receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f] quinoxaline-7-sulfonamide disodium salt, and a calcium permeable AMPA receptor antagonist, 1-naphthyl acetyl spermine. The D-serine reducing effects of (S)-AMPA are augmented by co-infusion of cyclothiazide that prevents AMPA receptor desensitization. Our data support the view that a calcium permeable AMPA receptor subtype may exert a phasic inhibitory control on the extracellular D-serine release in the mammalian prefrontal cortex in vivo.
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