| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
Repeated treatment with dexamethasone enhanced KCl-induced calcium rise in rat cortex slices, and lithium carbonate inhibited the enhancement. Repeated treatment with dexamethasone (1 mg/kg/day for 14 days) increased the density of 5-HT2A receptor, but not receptor in the rat frontal cortex. The density of 5-HT2A receptor in the rat frontal cortex was significantly increased 1 day after repeated treatment with dexamethasone, but was not increased 7 or 14 days after repeated treatment. Wet dog shakes (WDS) induced by DOI, a 5-HT2A receptor agonist, in rats were significantly enhanced 1, 7 and 14 day after repeated treatment with dexamethasone, although the frequency of WDS gradually decreased after repeated treatment. Repeated treatment with nimodipine (5 mg/kg/day for 14 days) attenuated DOI-induced WDS enhanced by repeated treatment with dexamethasone (1 mg/kg/day for 14 days), however, it did not change the density of 5-HT2A receptor. Repeated treatment with dexamethasone decreased l
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ocomotor activity and body weight, but repeated treatment with nimodipine did not recover these parometers. Furthermore, we found that brain-derived neurotrophic factor (BDNF) in rat brain treated with dexamethasone was decreased and that it was restored in rat brain treated with nimodipine.
Effect of prolonged pretreatment with serotonin (5-HT) on 5-HT2A receptor desensitization was examined by the measurement of intracellular calcium ([Ca2+]i) mobilization in cultured C6 glioma cells. 5-HT-induced desensitization of [Ca2+]i mobilization was in a time and dose dependent manner and reached a plateau after 3 hr. After 1 and 3 hr 5-HT pretreatment, 5-HT concentration in the medium little changed. 5-HT pretreatment with cycloheximide, a protein synthesis inhibitor, produced an enhancement of the desensitization for 3 and 6 hr pretreatmetnt. However, 5-HT pretreatment for 3 and 6 hr caused no marked change in the 5-HT2A receptor mRNA level or Gaq/11 protein in this study, suggesting that 5-HT may decrease 5-HT-induced [Ca2+]i mobilization independent of 5-HT2A receptor mRNA or G-proteins. Endothelin-1-induced [Ca2+]i mobilization did not alter after 5-HT and/or cycloheximide pretreatment. These results showed that activation of the 5-HT2A receptor induced homologous desensitization and pretreatment with 5-HT and/or cycloheximide did not change the efficacy of the second messenger pathway from Gq to a [Ca2+]i rise in C6 cells. In C6 cells, deprivation of fetal calf serum induced cell death of C6 cells, however, serotonin did not restored the cell death. Less
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