5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze

5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze
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DOI:
10.1523/jneurosci.19-14-06157.1999
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发表时间:
1999-07-15
影响因子:
5.3
通讯作者:
Buhot, MC
Buhot, MC
中科院分区:
医学1区
文献类型:
--
作者:
Malleret, G;Hen, R;Buhot, MC

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为了表征 5-HT1B 受体对行为的贡献,对 5-HT1B 敲除 (KO) 小鼠进行了一系列行为范式,旨在区分认知和情绪行为的各个组成部分。在物体探索任务中,野生型 (WT) 和 5-HT1B KO 小鼠的运动活动没有差异。然而,5-HT1B KO 小鼠表现出较低的趋触性(焦虑指数),与较高水平的物体探索活动相关,但在高架十字迷宫中没有观察到基因型差异。 5-HT1B KO 小鼠也表现出缺乏探索性习惯。在空间版本的莫里斯水迷宫中,5-HT1B KO小鼠在获取和转移测试中表现出更高的表现,而在视觉版本的任务中没有观察到这一点。在情境恐惧调节中没有发现基因型差异,因为 WT 和 5-HT1B KO 小鼠都能够记住它们接受厌恶刺激的情境。删除与适当的行为范式相关的 5-HT1B 受体,使我们能够将焦虑与对新奇事物的反应分开,将持久行为(缺乏习惯)与认知灵活性(水迷宫中的转移阶段)的适应性行为抑制分开。 5-HT1B 受体的缺失不会导致其他主要 5-HT 受体类型的显着发育可塑性,但可能影响其他神经传递系统。 5-HT1B 受体可能是血清素调节认知行为的关键靶标,特别是在涉及高认知需求的情况下。
In an attempt to characterize the contribution of the 5-HT1B receptor to behavior, 5-HT1B knock-out (KO) mice were subjected to a battery of behavioral paradigms aimed at differentiating various components of cognitive and emotional behaviors. In an object exploration task, wild-type (WT) and 5-HT1B KO mice did not differ in locomotor activity. 5-HT1B KO mice, however, displayed lower thigmotaxis (an index of anxiety) associated with a higher level of object exploratory activity, but no genotype differences were observed in the elevated plus maze. 5-HT1B KO mice also displayed a lack of exploratory habituation. In the spatial version of the Morris water maze, 5-HT1B KO mice showed higher performances in acquisition and transfer test, which was not observed in the visual version of the task. No genotype differences were found in contextual fear conditioning, because both WT and 5-HT1B KO mice were able to remember the context where they had received the aversive stimulus. The deletion of the 5-HT1B receptor, associated with appropriate behavioral paradigms, thus allowed us to dissociate anxiety from response to novelty, and perseverative behavior (lack of habituation) from adaptive behavioral inhibition underlying cognitive flexibility (transfer stage in the water maze). The deletion of the 5-HT1B receptor did not result in significant developmental plasticities for other major 5-HT receptor types but may have influenced other neurotransmission systems. The 5-HT1B receptor may be a key target for serotonin in the modulation of cognitive behavior, particularly in situations involving a high cognitive demand.