Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia
Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia
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DOI：
10.1016/s0166-4328(99)00063-7
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发表时间：
1999-10-01
影响因子：
2.7
通讯作者：
Blandina, P
中科院分区：
文献类型：
--
作者：
Giovannini, MG;Bartolini, L;Blandina, P
在以前的研究中，我们发现，训练前给予组胺H-3受体激动剂，如（R）-α-甲基组胺和imetit损害大鼠在物体识别和被动回避反应中的表现，在相同的剂量下，它们抑制了体内皮质乙酰胆碱的释放。相反，在本研究中，我们报告说，（R）-α-甲基组胺和imetit的训练后管理未能影响大鼠的性能在物体识别和被动回避反应，这表明H-3受体影响收购，而不是回忆过程。我们还研究了两种H-3受体拮抗剂，硫代哌丁胺和clobenpropit，在相同的行为任务的影响。训练前给予硫代哌丁胺和氯苄丙酸酯在正常动物中未表现出任何哌丁胺效应，但可预防东莨菪碱诱导的健忘症。然而，训练后给予硫代哌丁胺也可预防东莨菪碱诱导的健忘症。因此，通过H-3受体拮抗剂对东莨菪碱诱导的遗忘症的改善作用不仅通过解除皮质H-3受体的抑制作用介导，而且还涉及其他机制。然而，H-3受体拮抗剂可能对治疗与胆碱能功能受损相关的退行性疾病具有意义。(C)1999 Elsevier Science B. V.保留所有权利。
In previous research we found that pre-training administration of histamine H-3 receptor agonists such as (R)-alpha-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of (R)-alpha-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H-3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H-3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any precognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H-3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H-3 receptors, but other mechanisms are also involved. Nevertheless, H-3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function. (C) 1999 Elsevier Science B.V. All rights reserved.