Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1
Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1
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DOI：
10.1016/s0006-8993(98)01158-5
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发表时间：
1999-07-17
期刊：
影响因子：
2.9
通讯作者：
Gold, LH
中科院分区：
文献类型：
--
作者：
Contarino, A;Dellu, F;Gold, LH
促肾上腺皮质激素释放因子（CRF）已被假设参与焦虑，抑郁，认知和进食障碍的病理生理。两种不同的CRF受体亚型CRFR 1和CRFR 2被认为介导CNS中的CRF作用。然而，神经精神疾病的动物模型中的每个受体亚型的作用仍有待确定。使用CRFR 1缺陷小鼠，本研究调查了这种CRF受体亚型在焦虑样和记忆过程中的功能意义。CRFR 1基因敲除小鼠在高架十字迷宫（Elevated Plus-maze，EFL）和黑色和白色（B-W）焦虑测试箱模型中均表现出探索行为增加，表明CRFR 1基因缺失具有抗焦虑样作用。相比之下，在两次试验空间记忆任务的检索试验期间，野生型小鼠与Y迷宫装置的两个熟悉的臂相比，在新臂中进行了更多的访问并花费了更多的时间。未观察到CRFR 1缺陷小鼠探索新臂的水平增加。这表明CRFR 1基因敲除小鼠的空间识别记忆受损。这些结果表明，CRFR 1受体的遗传缺失可导致焦虑样和认知行为的损害，支持该受体在焦虑和认知生物学过程中的关键作用。(C)1999 Elsevier Science B. V.保留所有权利。
Corticotropin-releasing factor (CRF) has been hypothesized to be involved in the pathophysiology of anxiety, depression, cognitive and feeding disorders. Two distinct CRF receptor subtypes, CRFR1 and CRFR2, are thought to mediate CRF actions in the CNS. However, the role for each receptor subtype in animal models of neuropsychiatric disorders remains to be determined. Using CRFR1 deficient mice, the present study investigated the functional significance of this CRF receptor subtype in anxiety-like and memory processes. CRFR1 knockout mice displayed an increased exploratory behavior in both the Elevated Plus-maze (EPM) and the Black and White (B-W) test box models of anxiety, indicating an anxiolytic-like effect of the CRFR1 gene deletion. In contrast, during the retrieval trial of a two-trial spatial memory task wild type mice made more visits to and spent more time in the novel arm as opposed to the two familiar ones of a Y-maze apparatus. No increase in the level of exploration of the novel arm by the CRFR1 deficient mice was observed. This indicates that CRFR1 knockout mice are impaired in spatial recognition memory. These results demonstrate that genetic deletion of the CRFR1 receptor can lead to impairments in anxiety-like and cognitive behaviors, supporting a critical role for this receptor in anxiety and cognitive biological processes. (C) 1999 Elsevier Science B.V. All rights reserved.