Investigation of serotonergic regulation of acetycholine release in the cortex (II)

皮质中乙酰胆碱释放的血清素调节研究（II）

• 批准号: 10670902
• 负责人: HIRANO Hitoshi
• 金额: $ 2.05万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670902/
• 关键词: 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

〔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 … More 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

（实验）1)本文研究了5-羟色胺D21 A受体在肾上腺皮质投射胆碱能神经元的多巴胺能调节中的作用。8-OH-DPAT（DPAT ; 1.0 mg/kg，s.c.）显著增加皮质ACh输出。WAY 100-635（WAY ; 0.1 mg/kg，s.c.）不影响ACh输出。在额叶皮层局部应用WAY（0.1、10μM，60 min）对基础ACh输出无影响。在注射芬氟拉明（FEN ; 10 mg/kg，i. p.）或DOI（2.5mg/kg. i.p.）不影响ACh输出。然而，注射DOI后应用DPAT（10 μM）显著增强DOI增加皮质ACh释放的能力。在酮色林（KET ; 5 mg/kg，i. p.）未能影响ACh输出。这些结果表明了三种可能性。首先，5-HT可能不通过突触后5-HT受体D21 A受体D2紧张性刺激ACh释放。第二，FEN诱导的ACh释放增加可能主要通过5-HT受体D22 A受体D2介导。 ...更多信息 或第三，5-HT通过突触后5-HT受体D21 A受体D2对ACh释放的刺激作用可能在5-HT受体D22 A受体D2被激活时增强。（实验）2)研究了雌激素对皮质投射胆碱能神经元的影响。卵巢切除后19天，大鼠植入微透析探针，并立即皮下注射17β-雌二醇（3.0μg/kg. 30μg/kg、300μg/kg）或芝麻油。两天后进行微透析实验。17β-雌二醇处理导致每个单独动物组的血清雌二醇浓度之间存在显著差异。然而，它未能产生基础ACh输出的差异。此外，雌激素替代并没有产生差异，在FEN的能力，增加皮质乙酰胆碱释放。这些结果表明，雌激素替代两天不足以恢复皮质投射胆碱能神经元和5-HT受体D22 A受体D2的功能。少

项目成果

Hitoshi Hirano,Yoshito Matsuda Yoshibumi Watanabe,et al.: "Further experiment regarding the role of 5-HT_<1A> receptors in cortical acetylcholine release:mutual interaction between 5-HT_<2A> receptors and 5-HT_<1A> receptors"29th.Annual Meeting of Society

Hitoshi Hirano、Yoshito Matsuda Yoshibumi Watanabe 等人：“关于 5-HT_<1A> 受体在皮质乙酰胆碱释放中的作用的进一步实验：5-HT_<2A> 受体与 5-HT_<1A> 受体之间的相互作用”

Hitoshi Hirano,Yoshito Matsuda Hirata,et al.: "Serotonergic regulation of acetylcholine rilease in the frontal cortex(VI):Makizo Interaction of 5-HT_<2A> and 5-HT_3] receptors in cortical A Ch release"Neurochem.Res.. 24・1. 133 (1999)

Hitoshi Hirano、Yoshito Matsuda Hirata 等：“额叶皮质中乙酰胆碱释放的血清素调节 (VI)：皮质 A Ch 释放中 5-HT_<2A> 和 5-HT_3] 受体的 Makizo 相互作用”Neurochem.Res。 .24・1.133 (1999)

HITOSHI HIRANO, YOSHITO MATSUDA HIROSHI KANEYUKI, MAKIZO HIRATA: "Further experiment regarding role of 5-HTィイD23ィエD2 receptors in cortical acetylcholine release : Mutual interaction between 5-HTィイD22AィエD2 receptors and 5-HTィイD23ィエD2 receptors"28th. Annual

HITOSHI HIRANO、YOSHITO MATSUDA HIROSHI KANEYUKI、MAKIZO HIRATA：“关于 5-HTD23D2 受体在皮质乙酰胆碱释放中的作用的进一步实验：5-HTD22AD2 受体和 5-HTD2 受体 D23D2 受体之间的相互作用”，第 28 届年度报告。

Hitoshi Hirano、Yoshito Mastuda Yoshibumi Watanabe、et al.: "Serotonergic Reguration of acetylcholine release in the rat frontal cortex(V11):Interaction of 5-HT_<2A>and 5-HT_<え1A>receptors in cortical Ach release."Neurochem.Res.. In print.

Hitoshi Hirano、Yoshito Mastuda Yoshibumi Watanabe 等人：“大鼠额叶皮层 (V11) 中乙酰胆碱释放的血清素调节：皮质 Ach 释放中 5-HT_<2A> 和 5-HT_<e1A> 受体的相互作用。” .Res..印刷中。