| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In vivo brain microdialysis was applied to study the effect of N-methyl-D-aspartate (NMDA) on the extracellular concentrations of neurotransmitters (amino acide, dopamine and acetylcholine) in the hippocampus and striatum of awake freely moving rats.1) Systemic administration of NMDA (10-30 mg/kg, i.p.) , which induced a significant increase of taurine level, failed to facilitate the release of dopamine and other amino acids. 2) The local application (for 10 min) of NMDA does-dependently increased aspartate, glutamate, taurine and dopamine levels. Taurine was increased significantly by a low does (0.03 mM) of NMDA,while significant increases in aspartate, glutamate and dopamine were only observed when relatively high doses (>1 mM) of NMDA were applied. 3) The continuous infusion of NMDA (1 mM) via the microdialysis probe caused significant and marked increases of dopamine and amino acids (taurine, glutamate etc.) . Especially in the case of dopamine, desensitization was observed after
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1 hr of continuous application of NMDA.4) In the preaence of AP-5 (a NMDA antagonist ; 1 mM) , the effect of NMDA on both the taurine and dopamine was strongly inhibited. The effect of NMDA on dopamine was also inhibited by DNQX (a non-NMDA antagonist ; 0.1-0.3 mM) while the effect of NMDA on taurine was not affected by the treatment. The continuous infusion of alpha-amino-3-hudroxy-5-methyl-isoxazole-4-propionic acid (AMPA ; 1mM) , a non-NMDA agonist, also increased taurine and dopamine. The effect of AMPA was inhibited by the treatment of DNQX but not by the treatment of AP-5) . 5) The increasing effects of NMDA and AMPA on dopamine were diminished under the infusion of a hypertonic solution (+150 mM sucrose) while the effects of NMDA and AMPA on taurine were not affected by the treatment. 6) The continuous infusion of NMDA (1 mM) caused significant increase of acetylcholine level.7) These results suggest that NMDA receptor plays an important role in the regulation of extracellular neurotransmitter concentrations and that taurine is apparently sensitive to the local application of low dose NMDA than glutamate, dopamine etc.. These results also suggest that high concentrations of NMDA,which lead to increase a release of endogenous glutamate, act on dopamine via both NMDA and non-NMDA receptors and that the effect of NMDA might be related to cell swelling. Less
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