Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK-801 in rat brain by chronic infusion of subtoxic dose of MK-801

The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous...

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Veröffentlicht in:Neurochemical research 2001-05, Vol.26 (5), p.559-565
Hauptverfasser: OH, Seikwan, YOUNG HWA KIM, HOO JAE HANN, HEE LAI LEE, HONG SERCK CHOI, HACK SEANG KIM, ING KANG HO
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container_end_page 565
container_issue 5
container_start_page 559
container_title Neurochemical research
container_volume 26
creator OH, Seikwan
YOUNG HWA KIM
HOO JAE HANN
HEE LAI LEE
HONG SERCK CHOI
HACK SEANG KIM
ING KANG HO
description The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.
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Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>11513485</pmid><doi>10.1023/A:1010977315838</doi><tpages>7</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Dizocilpine Maleate - administration & dosage
Dizocilpine Maleate - metabolism
Dizocilpine Maleate - pharmacology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists - administration & dosage
Excitatory Amino Acid Antagonists - metabolism
Excitatory Amino Acid Antagonists - pharmacology
Fundamental and applied biological sciences. Psychology
Male
Protein Isoforms - genetics
Protein Isoforms - metabolism
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
RNA, Messenger - metabolism
Tissue Distribution
Tritium
Vertebrates: nervous system and sense organs
title Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK-801 in rat brain by chronic infusion of subtoxic dose of MK-801
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