CREBαδ- deficient mice show inhibition and low activity in novel environments without changes in stress reactivity
CREBαδ- deficient mice show inhibition and low activity in novel environments without changes in stress reactivity
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DOI：
10.1111/j.1460-9568.2004.03487.x
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Akil, H
中科院分区：
文献类型：
--
作者：
Hebda-Bauer, EK;Watson, SJ;Akil, H
对意外或新奇刺激做出反应的能力对生存至关重要。确定一种刺激确实是新奇的，需要记忆来确定它缺乏熟悉性。由于参与记忆形成的长期突触变化需要cAMP反应元件结合蛋白(CREB)，我们研究了CREB参与对新环境的反应的程度。这些环境通常会触发内分泌应激反应。因此，我们通过定向干扰CREB基因的阿尔法和德尔塔亚型(CREBalphaDelta缺陷小鼠)，测量了小鼠对三种新环境和一种熟悉环境的行为和应激激素反应。我们发现CREBalphaDelta缺陷小鼠在高架加迷宫、开阔场地和明/暗盒子中不那么活跃，更受抑制，没有表现出焦虑样行为的差异。这种抑制是新环境中独有的，因为这些小鼠在熟悉的环境--笼子里表现出正常的表型。尽管CREBalphaDelta缺陷小鼠在新的环境中表现出行为变化，但它们对轻度和中度应激表现出正常的反应，因为皮质酮的基础和应激水平都与野生型对照组相似。这是CREWalphaDelta缺陷小鼠的第一份报告：(I)在最初暴露于环境时表现出与学习和记忆相关的行为无关的改变行为，(Ii)作为一种动物模型，可以在新的环境中将运动活动与类似焦虑的行为分开。
The ability to respond to unexpected or novel stimuli is critical for survival. Determining that a stimulus is indeed novel requires memory to ascertain its lack of familiarity. As the long-term synaptic changes involved in memory formation require the cAMP response element binding protein (CREB), we examined the extent to which CREB is involved in responses to novel environments. These environments typically trigger an endocrine stress response. Thus, we measured behavioural and stress hormone responses to three novel and one familiar environment in mice with a targeted disruption of the alpha and delta isoforms of the CREB gene (CREBalphadelta- deficient mice). We found CREBalphadelta- deficient mice to be less active and more inhibited in the elevated plus maze, open field, and light/dark box, without showing differences in anxiety-like behaviour. This inhibition is unique to novel environments because these mice display a normal phenotype in the home cage, a familiar environment. Although CREBalphadelta- deficient mice exhibit altered behaviour in novel environments, they show normal reactivity to mild and moderate stress as both basal and stress levels of corticosterone are similar to those of wild-type controls. This is the first report of CREWalphadelta- deficient mice to: (i) show altered behaviour, not related to learning and memory-associated behaviours, upon initial exposure to environments and (ii) serve as an animal model that can dissociate locomotor activity from anxiety-like behaviour in novel environments.