Project/Area Number |
10670902
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Yamaguchi University |
Principal Investigator |
HIRANO Hitoshi Health Administration Center, Yamaguchi University, Associate Professor, 保健管理センター, 助教授 (70228807)
|
Co-Investigator(Kenkyū-buntansha) |
小林 孝吉 山口大学, 医学部・附属病院, 医員
TAKAMATSU Norio Department of Neuropsychiatry, Yamaguchi University, Senior Resident, 医学部・附属病院, 医員 (40304480)
HIRATA Makizo Health Administration Center, Yamaguchi University, Professor, 保健管理センター, 教授 (10156672)
ABE Masaaki Department of Neuropsychiatry, Yamaguchi University, Senior Resident, 医学部・附属病院, 医員
KOBAYASHI Kokichi Department of Neuropsychiatry, Yamaguchi University, Senior Resident
安部 公朗 山口大学, 医学部・附属病院, 医員
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | acetylcholine release / cerebral cortex / serotonergic neuronal system / serotonin 1A receptors / serotonin 2A receptors / cortically projecting cholinergic neurons / estrogen / brain microdialysis / fenfluramine / 脳微少透析法 |
Research Abstract |
〔Exp. 1〕 The role of 5-HTィイD21AィエD2 receptors in the serotonergic regulation of cortically projecting cholinergic neurons was studied. 8-OH-DPAT (DPAT ; 1.0 mg/kg, s.c.) significantly increased cortical ACh output. WAY 100-635 (WAY ; 0.1 mg/kg, s.c.) did not influence the ACh output. Local application of WAY (0.1, 10μM for 60 min) in the frontal cortex had no effect on the basal ACh output. Locally applied WAY (10 μM for 60 min) after injection of fenfluramine (FEN ; 10 mg/kg, i.p.) or DOI (2.5 mg/kg. i.p.) did not affect the ACh output. Nevertheless, DPAT (10 μM) applied after injection of DOI significantly potentiated DOI's ability to increase cortical ACh release. DPAT injected after ketanserin (KET ; 5 mg/kg, i.p.) failed to affect the ACh output. These results suggest three possibilities. First, 5-HT may not tonically stimulate ACh release via the postsynaptic 5-HTィイD21AィエD2 receptors. Second, FEN-induced increase of ACh release may be mediated mainly via the 5-HTィイD22AィエD2 recept
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ors. Third, the stimulatory effect of 5-HT on ACh release via the postsynaptic 5-HTィイD21AィエD2 receptors may be increased when the 5-HTィイD22AィエD2 receptors are activated. 〔Exp. 2〕 The effects of estrogen on cortically projecting cholinergic neurons were investigated. Nineteen days after ovariectomy rats were implanted a microdialysis probe, and immediately injected subcutaneously with either 17β-estradiol (3.0μg/kg. 30μg/kg, 300μg/kg), or sesame oil. Two days later microdialysis experiment was performed. 17β-estradiol treatment resulted in a significant difference among the serum estradiol concentrations of each individual animal group. However, it failed to produce a difference in the basal ACh output. In addition, estrogen replacement did not yield a difference in FEN's ability to increase cortical ACh release. These results suggest that estrogen replacement for two days is not enough to restore both the functions of cortically projecting cholinergic neurons, and of 5-HTィイD22AィエD2 receptors. Less
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