Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior
Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior
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DOI：
10.1016/j.euroneuro.2011.05.007
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发表时间：
2012-01-01
影响因子：
5.6
通讯作者：
Lichtstein, David
中科院分区：
文献类型：
--
作者：
Goldstein, Inbal;Lax, Elad;Lichtstein, David
抑郁症是世界上最严重的公共卫生问题之一。 Na+、K+-ATP 酶是类固醇洋地黄类化合物 (DLC) 的既定受体。在抑郁症中检测到大脑 Na-+、Na-K+-ATP 酶和 DLC 的改变，提出了它们参与这些病理学的假设。本研究旨在通过研究在正常斯普拉格道利 (SD) 和遗传性抑郁大鼠的弗林德斯敏感线 (FSL) 中，通过抗哇巴因抗体给药而实现的大脑 DLC 活性中和的行为和生化后果，进一步阐述这一假设。慢性静脉注射对 FSL 大鼠施用抗哇巴因抗体可引发抗抑郁行为。对SD大鼠脑室内注射抗哇巴因抗体可显着改变海马、腹侧被盖和伏核中儿茶酚胺及其代谢物的水平。这些结果与内源性 DLC 可能与抑郁症的表现有关的观点一致，并表明其水平的改变可能具有重要的治疗价值。 (C) 2011 Elsevier B.V. 和 ECNP。版权所有。
Depressive disorders are among the world's greatest public health problems. Na+, K+-ATPase is the established receptor for the steroidal digitalis-like compounds (DLC). Alteration in brain Na-+,Na- K+-ATPase and DLC have been detected in depressive disorders raising the hypothesis of their involvement in these pathology. The present study was designed to further elaborate this hypothesis by investigating the behavioral and biochemical consequences of neutralization in brain DLC activity attained by anti-ouabain antibodies administrations, in normal Sprague Dawley (SD) and in the Flinders Sensitive Line (FSL) of genetically depressed rats. Chronic i.c.v. administration of anti-ouabain antibodies to FSL rats elicited anti-depressive behavior. Administration of anti-ouabain antibodies intracerebroventriculary (i.c.v.) to SD rats significantly changed the levels of catecholamines and their metabolites in the hippocampus, ventral tegmentum and nucleus accumbence. These results are in accordance with the notion that endogenous DLC may be involved in the manifestation of depressive disorders and suggests that alteration in their levels may be of significant therapeutic value. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.