Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning
Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning
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DOI：
10.1016/s0306-4530(97)00091-7
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发表时间：
1998-01-01
影响因子：
3.7
通讯作者：
Luiten, PGM
中科院分区：
文献类型：
--
作者：
Douma, BRK;Korte, SM;Luiten, PGM
来自肾上腺皮质的皮质类固醇影响各种行为，包括认知、学习和记忆。这些激素通过两种细胞内受体起作用，盐皮质激素受体（MR）和糖皮质激素受体（GR）。这两种受体类型在海马中显示出高浓度和不同的分布，海马是直接参与空间定向和学习调节的脑区。在这项研究中，重复皮下注射盐皮质激素受体拮抗剂RU 28318（1.0 mg/100 g体重），糖皮质激素受体阻滞剂RU 38486（2.5毫克/100克体重），或两种拮抗剂的组合研究了它们对工作的影响，在随后的8天中，在上午和下午的试验中，食物中的参考记忆在孔板任务中奖励空间学习。在训练第1、3、5和7天的第一次试验后，每只大鼠直接接受一剂媒介物（PEG 400中的2%乙醇）、RU 28318、RU 38486或两种拮抗剂的组合。实验表明，盐皮质激素受体的反复阻断损害参考记忆反映在早上，以及在下午的审判，而糖皮质激素受体的阻断对这种类型的认知行为几乎没有影响。此外，MR和GR的组合阻断导致在两个日常试验中参考记忆和工作记忆表现的降低。这些研究结果表明，在这种空间学习范式，工作记忆的损害需要两种受体类型的封锁，而参考记忆性能主要涉及盐皮质激素受体。(C)1998爱思唯尔科技有限公司版权所有。
Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and distinct distribution in the hippocampus, a brain region which is directly involved in the regulation of spatial orientation and learning. In this study, repeated subcutaneous administration of the mineralocorticoid receptor antagonist RU28318 (1.0 mg/100 g body weight), the glucocorticoid receptor blocker RU38486 (2.5 mg/100 g body weight), or a combination of both antagonists were investigated for their effects on working-and reference memory in morning and afternoon trials during 8 subsequent days in food rewarded spatial learning in a hole board task. Each rat received one dose of either vehicle (2% ethanol in PEG 400), RU28318, RU38486 or the combination of both antagonists directly after the first trial on training days 1, 3, 5, and 7. The experiments demonstrated that repeated blockade of mineralocorticoid receptors impairs reference memory reflected in the morning-as well as in the afternoon trial, whereas blockade of glucocorticoid receptors has little effect on this type of cognitive behaviour. Furthermore, combined blockade of MRs and GRs resulted in a decrease, in both daily trials, in reference memory as well as working memory performance. These findings suggest that in this spatial learning paradigm, the impairment of working memory required blockade of both receptor types, while reference memory performance involves predominantly the mineralocorticoid receptors. (C) 1998 Elsevier Science Ltd. All rights reserved.