The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze
The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze
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DOI：
10.1016/j.peptides.2006.11.002
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发表时间：
2007-03-01
期刊：
影响因子：
3
通讯作者：
Motamedi, Fereshteh
中科院分区：
文献类型：
--
作者：
Akbari, Esmaeil;Naghdi, Nasser;Motamedi, Fereshteh
新的神经肽orexin-A和orexin-B来自一个共同的130个氨基酸的前体分子（prepro-orexin），主要定位于神经元内和周围的外侧下丘脑，并表现出高亲和力的密切相关的G蛋白偶联受体orexin 1和2受体（OX 1 R，OX 2 R）。Orexinergic神经元将其轴突发送到表达OX（1）Rs的海马结构（CA 1、CA 2和齿状回）。最近的研究表明，食欲素-A和食欲素-B的中枢给药对学习和记忆有影响，但关于食欲素能系统在认知中的作用的文献仍然存在争议。最近，已经描述了拮抗剂。最有效和选择性的是SB-334867-A，其对OX 1 R的亲和力为40 nM，其选择性至少是OX 2 R的50倍。很可能脑室内（i. c. v.）给药可阻断许多脑区的OX（1）受体。先前我们已经表明，CA 1内注射SB-334867-A会损害MWM任务中空间记忆的获取、巩固和检索。在本研究中，检查了SB-334867-A（1.5、3、6 μ g/0.5 μ l）试验DG（齿状回）内给药的训练前、训练后和探测前对MWM（Morris水迷宫）任务单日测试版本中获取、巩固和检索的影响。我们的研究结果显示，与对照组相比，SB-334867-A的MWM任务获得和巩固受损。然而，SB-334867-A对空间记忆的提取没有影响。此外，这种拮抗剂对非空间视觉辨别任务的逃避潜伏期没有影响。因此，内源性orexin-A和orexin-B可能通过DG OX（1）Rs在大鼠空间学习记忆中发挥重要作用。(c)2006年爱思唯尔公司All rights reserved.
The novel neuropeptides orexin-A and orexin-B derive from a common 130-amino acid precursor molecule (prepro-orexin), are mainly localized to neurons within and around the lateral hypothalamus, and exhibit high affinity to the closely related G-Protein-coupled receptors orexin 1 and 2 receptor (OX1R, OX2R). Orexinergic neurons send their axons to the hippocampal formation (CA1, CA2 and dentate gyrus), which expresses OX(1)Rs. Recent studies have shown that central administration of orexin-A and orexin-B have effects on learning and memory but literature concerning the role of orexinergic system in cognition remains controversial. More recently, antagonists have been described. The most potent and selective is SB-334867-A, which has an affinity of 40 nM at OX1R which is at least 50-fold selective over OX2R. It is likely that the intracerebroventricular (i.c.v.) administration may block OX(1)Rs in many brain regions. Previously we have shown that intra-CA1 injection of SB-334867-A impairs acquisition, consolidation and retrieval of spatial memory in MWM task. In the present study, the effect of pre-training, post-training and pre-probe of trial intra-DG (dentate gyrus) administration of SB-334867-A (1.5, 3, 6 mu g/0.5 mu l) on acquisition, consolidation and retrieval in a single-day testing version of MWM (Morris water maze) task was examined. Our results show impaired acquisition and consolidation of MWM task for SB-334867-A as compared with the control group. However, SB-334867-A had no effect on retrieval in spatial memory. Also, this antagonist had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexin-A and orexin-B, through DG OX(1)Rs, play an important role in spatial learning and memory in the rat. (c) 2006 Elsevier Inc. All rights reserved.