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静脉注射8-羟基-2-(二丙基氨基)四氢萘后,5-羟色胺1A受体和α2受体参与大鼠视交叉上核中5-羟色胺释放和代谢的降低。

Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin.

作者信息

Marsden C A, Martin K F

出版信息

Br J Pharmacol. 1986 Oct;89(2):277-86. doi: 10.1111/j.1476-5381.1986.tb10257.x.

Abstract

The 5-hydroxytryptamine1A-receptor agonist 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT, 0.1 mg kg-1 i.v.) decreased the height of the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry. The decrease in extracellular 5-HIAA produced by 8-OH-DPAT could be partially attenuated by prior administration of the non-selective 5-HT receptor antagonist methiothepin (1 mg kg-1 i.v.). The 5-HT2-receptor antagonist ritanserin (0.2 mg kg-1 i.v.) did not appear to block the effects of 8-OH-DPAT. The selective ligand for 5-HT1A recognition sites TVX Q 7821 (isapirone, 1 mg kg-1 i.v.) decreased the extracellular level of 5-HIAA in the SCN but to a lesser extent than 8-OH-DPAT. The response to 8-OH-DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8-OH-DPAT. Idazoxan (0.2 mg kg-1 i.v.) an alpha 2-adrenoceptor antagonist, completely blocked the effect of 8-OH-DPAT on the 5-HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5-HIAA oxidation peak when given alone. At a dose of 0.5 mg kg-1 i.v. idazoxan induced a 120% increase in the height of the indole oxidation peak, suggesting that 5-HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs. The data in this paper suggest that 5-HT1A- and alpha 2-receptors are involved in the effects of i.v. administered 8-OH-DPAT on 5-HT release and metabolism in the SCN in vivo.

摘要

5-羟色胺1A受体激动剂8-羟基-2-(二丙基氨基)四氢萘(8-OH-DPAT,0.1毫克/千克静脉注射),通过微分脉冲伏安法,降低了麻醉大鼠视交叉上核(SCN)中记录到的细胞外5-羟吲哚乙酸(5-HIAA)氧化峰的高度。8-OH-DPAT引起的细胞外5-HIAA的降低,可被预先给予的非选择性5-羟色胺(5-HT)受体拮抗剂甲硫哒嗪(1毫克/千克静脉注射)部分减弱。5-HT2受体拮抗剂利坦色林(0.2毫克/千克静脉注射)似乎并未阻断8-OH-DPAT的作用。5-HT1A识别位点的选择性配体TVX Q 7821(伊沙匹隆,1毫克/千克静脉注射)降低了SCN中5-HIAA的细胞外水平,但程度小于8-OH-DPAT。预先给予TVX Q 7821后,对8-OH-DPAT的反应减弱至一定水平,表明TVX Q 7821阻断了静脉注射8-OH-DPAT的作用。α2-肾上腺素能受体拮抗剂咪唑克生(0.2毫克/千克静脉注射)完全阻断了8-OH-DPAT对SCN中记录到的5-HIAA氧化峰的作用,而单独给药时对5-HIAA氧化峰无影响。静脉注射剂量为0.5毫克/千克时,咪唑克生使吲哚氧化峰高度增加120%,表明大鼠SCN中的5-羟色胺释放和代谢可能受紧张性肾上腺素能输入的影响。本文数据表明,5-HT1A和α2受体参与了静脉注射8-OH-DPAT对体内SCN中5-羟色胺释放和代谢的作用。

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