| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
We have studied the expression of serine racemase, catalyzing D-serine, and D-amino acid oxidas, metabolizing D-serine, in rat brain after acute administration of morphine.
1) Acute morphine administration (10, 20, 40 mg/kg, ip) induced the mRNA expressions of serine racemase and D-amino acid oxidase 4 hours after administration.
2) Serine racemase mRNA could be demonstrated predominantly in neurons of rat brain by application of in situ hybridization.
3) Repeated administration of morphine for 30 days produced a significant augmentation of both the mRNA and protein expressions of serine racemase in all the brain regions, whereas no significant change in the protein expression of D-amino acid oxidase was observed in all the brain regions. Furthermore, the chronic administration caused a slight but significant elevation in the concentration of D-serine in the cortex, striatum, and hippocampus.
4)The intracerebroventricular administration of midazolam alone produced hyperalgesia on the tail-flick response in a benzodiazepine receptor antagonist, flumazenil-reversible manner. The antinociception induced by the intracerebroventricular application of D-serine or morphine was attenuated by the intracerebroventricular administration of midazolam. In addition, this inhibitory effect of midazolam on the dntinociception of D-serine or morphine was antagonized by the intracerebroventricular administration of flumazenil.
Together with the facts that D-serine and midazolam act as selective agonists for the glycine site of the N-methyl-D-aspartate receptor and benzodiazepine/GABAA receptor, respectively, these observations suggest a functional interaction between the NMDA and benzodiazepine/GABAA receptors in the regulation of antinociception at the supraspinal level.
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