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兴奋性氨基酸受体拮抗剂可阻断大鼠基底外侧杏仁核中γ-氨基丁酸A受体阻断所引发的心血管和焦虑反应。

Excitatory amino acid receptor antagonists block the cardiovascular and anxiety responses elicited by gamma-aminobutyric acidA receptor blockade in the basolateral amygdala of rats.

作者信息

Sajdyk T J, Shekhar A

机构信息

Department of Psychitry, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

出版信息

J Pharmacol Exp Ther. 1997 Nov;283(2):969-77.

PMID:9411030
Abstract

Blockade of gamma-aminobutyric acid (GABAA) receptors in the anterior basolateral amygdala (BLA) with bicuculline methiodide results in an increase in heart rate, blood pressure and "anxiety" in rats. Glutamate receptors in the BLA are also reported to be involved in eliciting anxiety responses. The purpose of this study was to investigate the interaction between GABAergic inhibition and glutamatergic excitation in the BLA. Male Wistar rts were implanted with femoral arterial catheters and bilateral chronic microinjection cannulae into the BLA. Each animal was injected with either artificial cerebrospinal fluid (100 nl), bicuculline methiodide (10 pmol/100 nl) or bicuculline methiodide + one dose of an antagonist of either the N-methyl-D-aspartate receptor [AP5 (20 and 100 pmol) and dizocilpine (25 and 125 pmol)] or the non-N-methyl-D-aspartate ionotropic receptor [CNQX (10 and 50 pmol) and GYKI 52466 (50 and 250 pmol)]. Increases in heart rate, blood pressure and "anxiety" (as measured in the social interaction test) observed in rats after bicuculline methiodide injections into the BLA were blocked in a dose dependent manner with the concurrent injections of either N-methyl-D-aspartate or non-N-methyl-D-aspartate antagonists, suggesting that activation of both subtypes of glutamate ionotropic receptors may be necessary for the responses elicited by GABAA receptor blockade in the basolateral amygdala.

摘要

用甲硫酸荷包牡丹碱阻断大鼠前基底外侧杏仁核(BLA)中的γ-氨基丁酸(GABAA)受体会导致心率、血压升高以及大鼠出现“焦虑”症状。据报道,BLA中的谷氨酸受体也参与引发焦虑反应。本研究的目的是调查BLA中GABA能抑制和谷氨酸能兴奋之间的相互作用。雄性Wistar大鼠植入股动脉导管,并在BLA双侧植入慢性微量注射套管。每只动物注射人工脑脊液(100 nl)、甲硫酸荷包牡丹碱(10 pmol/100 nl)或甲硫酸荷包牡丹碱 + 一剂N-甲基-D-天冬氨酸受体拮抗剂[AP5(20和100 pmol)及地佐环平(25和125 pmol)]或非N-甲基-D-天冬氨酸离子型受体拮抗剂[CNQX(10和50 pmol)及GYKI 52466(50和250 pmol)]。在向BLA注射甲硫酸荷包牡丹碱后,大鼠出现的心率、血压升高以及“焦虑”(通过社交互动测试测量),在同时注射N-甲基-D-天冬氨酸或非N-甲基-D-天冬氨酸拮抗剂时以剂量依赖方式被阻断,这表明谷氨酸离子型受体的两种亚型的激活可能是基底外侧杏仁核中GABAA受体阻断引发反应所必需的。

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