Effects of Stress on Brain Neuronal Network and Modification of Benzodiazepines and Nitrous Oxide

压力对脑神经网络的影响以及苯二氮卓类药物和一氧化二氮的修饰

• 批准号: 10671901
• 负责人: KAWAHARA Hiroshi
• 金额: $ 1.66万
• 依托单位: Kyushu Dental College
• 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-10671901/
• 关键词: MICRODIALYSIS; BENZODIAZEPINE ANXIOLYTICS; MIDAZOLAM; NORADRENERGIC NEURON; LOCUS COERULEUS; PREFRONTAL CORTEX; STRESS; AUTO RECEPTOR

Dual-probe microdialysis was used to investigate the release of noradrenaline in the medial prefrontal cortex (mPFC) during stress. Male albino rats of a Wistar-derived strain were used for the experiments. For that purpose a micro-dialysis probe was implanted in the vicinity of the locus coeruleus (LC) and a second probe was placed in the ipsilateral PFC. Receptor specific antagonists acting in the αィイD22ィエD2 adrenoceptor (idazoxane). GABAィイD2AィエD2 (bicuculline), GABAィイD2BィエD2 (CGP52432), acetylacholine (atropine), corticotropine releasing factor (CRF) (CP 154,526), NMDA glutamate (CPP), non-NMDA glutamate Receptor (DNQX) were infused into the LC by retrograde dialysis, whereas extracellular NA was recorded in the ipsilateral PFC. During infusion of the various compounds rat were gently handled for 10 min.Infusion of idazoxane potentiates the handling-induced increase in the release of NA in the PFC. Infusion of atropine, bicuculline CGP52432 and DNQX were without effect in the handling response. Infusion of the non-peptide CRF antagonist CP 154,526 and CPP suppressed the simulation of NA during handling stress, and benzodiazepine anxiolytic (midazolam) also suppressed.It is concluded that αィイD22ィエD2, NMDA glutamate and CRF receptors modify the handling stress response of LC neurons, and benzodiazepine anxiolytics also modify it. These data suggest no major role for GABAergic, nor cholinergic affernts to the LC in mediating the stress response.

采用双探针微透析技术研究了应激时内侧前额叶皮质（mPFC）去甲肾上腺素的释放。将Wistar衍生品系的雄性白化病大鼠用于实验。为此目的，将微透析探针植入蓝斑（LC）附近，并将第二个探针放置在同侧PFC中。受体特异性拮抗剂作用于α受体D22受体D2肾上腺素受体（咪唑烷）。GABA受体D2 A受体D2（荷包牡丹碱），GABA受体D2 B受体D2（CGP 52432），乙酰胆碱（阿托品）、促肾上腺皮质激素释放因子（CRF）通过逆行透析向LC中注入CP 154，526、NMDA谷氨酸（CPP）、非NMDA谷氨酸受体（DNQX），而细胞外NA记录在同侧PFC中。在输注各种化合物期间，轻轻处理大鼠10分钟。阿托品、荷包牡丹碱、CGP 52432和DNQX对处理反应无影响。输注非肽类CRF拮抗剂CP 154，526和CPP抑制了处理应激期间NA的刺激，苯二氮卓类抗焦虑药结论：α-氨基丁酸D22受体、NMDA谷氨酸受体和CRF受体改变LC神经元的应激反应，苯二氮类抗焦虑药也改变LC神经元的应激反应。也没有胆碱能对LC介导应激反应的影响。

项目成果

Kawahara H. Kawahara Y, Westerink BHC: "The role of afferents of the locus coeruleus in the handling stress-induced increase in the release of noradrenaline in the medial prefrontal cortex : a dual-probe microdialysis study in the rat brain"European Journ

Kawahara H. Kawahara Y，Westerink BHC：“蓝斑传入神经在处理应激引起的内侧前额皮质去甲肾上腺素释放增加中的作用：大鼠大脑中的双探针微透析研究”欧洲期刊

Kawahara Y,Kawahara H,Westerink BHC: "The role of afferents to the locus coeruleus in the handling stress-induced increase in the release of noradrenaline in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain"European Journal

Kawahara Y、Kawahara H、Westerink BHC：“蓝斑传入神经在处理应激引起的内侧前额皮质去甲肾上腺素释放增加中的作用：大鼠大脑中的双探针微透析研究”欧洲杂志

Kawahara Y, Kawahara H, Westerink BHC: "Comparison of effects of hypotension and handling stress on the release of nor adrenaline and dopamine in the locus coeruleus and medial prefrontal cortex of the rat"Naunyn-Schmiedeberg's Archives of Pharmacology. 3

Kawahara Y、Kawahara H、Westerink BHC：“低血压和处理应激对大鼠蓝斑和内侧前额皮质中去甲肾上腺素和多巴胺释放的影响比较”Naunyn-Schmiedeberg 药理学档案。

河原 博,河原幸江 今村佳樹,仲西 修: "脳内ノルアドレナリン神経活動へのα_2,GABA_A,グルタミン酸受容体作動薬の作用" 日本麻酔・薬理学会雑誌. 11(2). 21-25 (1998)

Hiroshi Kawahara、Yukie Kawahara、Yoshiki Imamura 和 Osamu Nakanishi：“α_2、GABA_A 和谷氨酸受体激动剂对大脑去甲肾上腺素能神经活动的影响”日本麻醉学和药理学会杂志 11-25。 (1998)