title: Modulation of extracellular d-serine content by calcium permeable AMPA receptors in rat medial prefrontal cortex as revealed by in vivo microdialysis.
abstract: 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 α-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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Ishiwata
authors.forename: Asami
authors.initials: A
authors.lastname: Umino
authors.forename: Masakazu
authors.initials: M
authors.lastname: Umino
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yorita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukui
authors.forename: Toru
authors.initials: T
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001581:Benzothiadiazines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D005470:Fluorometry; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D001581:Benzothiadiazines; D018683:Excitatory Amino Acid Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C067506:1-naphthylacetylspermine; D013096:Spermine; D012694:Serine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C004639:cyclothiazide