Recapitulation and reversal of a persistent depression-like syndrome in rodents.
Recapitulation and reversal of a persistent depression-like syndrome in rodents.
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DOI：
10.1002/0471142301.ns0932s49
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发表时间：
2009-10
影响因子：
--
通讯作者：
Taylor, Jane R
中科院分区：
文献类型：
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作者：
Gourley, Shannon L;Taylor, Jane R
多种生物学功能（如转录因子活性）的改变与抑郁症的神经生物学有关，这主要是基于对幼稚啮齿类动物抗抑郁疗效的表征，而不是基于捕捉抑郁症典型的快感缺乏和无助感的模型。为了解决这个问题，作者在大鼠和小鼠中开发了一种方案，要求长期口服暴露于应激相关的肾上腺激素皮质酮（CORT），导致快感缺乏和类似于抑郁的行为，这些行为是持久的，但通过长期抗抑郁治疗是可逆的。先前的CORT暴露也会长期影响被假设为有助于消极情绪的分子靶点：一个例子是海马和丘脑核中cAMP反应元件结合蛋白的磷酸化。先前的慢性CORT暴露提供了慢性轻度应激抑郁模型的替代方法，该模型易于复制并且在CORT暴露期之后持续很长时间，从而对人类的持续性抑郁样状态进行建模。
Alterations in multiple biological functions, such as transcription factor activity, are implicated in the neurobiology of depression based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the protracted feelings of anhedonia and helplessness that typify depression. In order to address this issue, the authors developed protocols in rats and mice calling for chronic oral exposure to the stress-associated adrenal hormone, corticosterone (CORT), resulting in anhedonic- and helplessness-like behaviors that are persistent yet reversible by chronic antidepressant treatment. Prior CORT exposure also chronically influences molecular targets hypothesized to contribute to negative mood: One example is phosphorylation of cAMP Response Element Binding protein in the hippocampus and nucleus accumbens. Prior chronic CORT exposure provides an alternative method to chronic mild stress models of depression that is easily replicable and persists well beyond the CORT exposure period, thereby modeling the persistent depressive-like state in man.