Compartmentation of alpha 1 and alpha 2 GABAA receptor subunits within rat extended amygdala:: implications for benzodiazepine action

Compartmentation of alpha 1 and alpha 2 GABAA receptor subunits within rat extended amygdala:: implications for benzodiazepine action
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DOI:
10.1016/s0006-8993(02)04082-9
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发表时间:
2003-02-21
期刊:
影响因子:
2.9
通讯作者:
Marksteiner, J
Marksteiner, J
中科院分区:
医学3区
文献类型:
--
作者:
Kaufmann, WA;Humpel, C;Marksteiner, J

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扩展的杏仁核是基底前脑内的形态和功能实体,是恐惧和焦虑等情绪状态的神经元基质。焦虑症通常通过苯二氮卓类药物治疗,苯二氮卓类药物通过 GABA A 受体介导其作用。苯二氮卓类药物的结合特性和作用取决于异五聚体受体的 α 亚基特征:α1 亚基与 I 型苯二氮卓类药理学相关,据报道介导苯二氮卓类药物的镇静和遗忘作用,而 α2 亚基赋予苯二氮卓类 II 型药理学并介导苯二氮卓类药物的抗焦虑作用。我们确定了扩展杏仁核内α1和α2亚基的定位,通过分泌神经素免疫染色鉴定,以确定不同苯二氮卓作用的形态底物。在内侧分区的区室中可以检测到 α1 亚基的中等表达,而在整个中央分区中可以检测到 α2 亚基的强表达。结论是,α1 和 α2 亚基在扩展杏仁核内差异表达,表明该结构在功能和苯二氮卓作用方面是分开的。 (C) 2002 Elsevier Science B.V. 保留所有权利。
The extended amygdala, a morphological and functional entity within the basal forebrain, is a neuronal substrate for emotional states like fear and anxiety. Anxiety disorders are commonly treated by benzodiazepines that mediate their action via GABA A receptors. The binding properties and action of benzodiazepines depend on the alpha-subunit profile of the hetero-pentameric receptors: whereas the alpha1 subunit is associated with benzodiazepine type I pharmacology and reportedly mediates sedative as well as amnesic actions of benzodiazepines, the alpha2 subunit confers benzodiazepine type II pharmacology and mediates the anxiolytic actions of benzodiazepines. We determined the localization of alpha1 and alpha2 subunits within the extended amygdala, identified by secretoneurin immunostaining, to define the morphological substrates for the diverse benzodiazepine actions. A moderate expression of the alpha1 subunit could be detected in compartments of the medial subdivision and a strong expression of the alpha2 subunit throughout the central subdivision. It is concluded that the alpha1 and alpha2 subunits are differentially expressed within the extended amygdala, indicating that this structure is compartmentalized with respect to function and benzodiazepine action. (C) 2002 Elsevier Science B.V. All rights reserved.