Effect of 5-HT7 antagonist SB-269970 in the modulation of working and reference memory in the rat
Effect of 5-HT7 antagonist SB-269970 in the modulation of working and reference memory in the rat
复制标题
DOI：
10.1016/j.bbr.2007.12.020
复制
发表时间：
2008-12-16
影响因子：
2.7
通讯作者：
Meneses, Alfredo
中科院分区：
文献类型：
--
作者：
Gasbarri, Antonella;Cifariello, Agata;Meneses, Alfredo
已经确定，血清素能途径投射到涉及学习和记忆的大脑区域，血清素（5-HT）受体激动剂和拮抗剂改变了这些过程。事实上，目前已知的大多数5-HT受体，即5-HT1至5-HT7，在大脑海马区、杏仁核和皮层等与学习和记忆有关的区域均有区域分布。虽然5-HT7受体的生物学功能尚不清楚，但最近有人认为它可能在控制学习和记忆过程中发挥作用。本研究的目的是评估5-HT7受体拮抗剂SB-269970对桡臂迷宫任务中工作记忆和参考记忆的作用，采用两阶段程序，包括获取和测试阶段，分别评估工作记忆和参考记忆。我们的研究结果表明，5-HT7受体拮抗剂SB-269970改善了记忆，减少了测试阶段的错误次数，从而影响了参考记忆，而对工作记忆没有影响。考虑到5-HT7受体在中枢神经系统中的特定定位，可以解释这些结果。事实上，在HF中发现了高浓度的5-HT7受体，它在参考记忆中发挥重要作用，而在参与工作记忆的前额叶皮层中存在相对较低的浓度。因此，当学习任务涉及高难度时，5-HT7受体阻断具有前认知效应。这一结论在5-HT受体在失忆症（如阿尔茨海默病）或学习复杂时发挥重要作用的背景下具有重要意义。(C) 2008 Elsevier B.V.版权所有
It has been established that serotonergic pathways project to cerebral areas involved in learning and memory and that serotonin (5-HT) receptor agonists and antagonists modify these processes. Indeed, most of the 5-HT receptors characterized so far, i.e., 5-HT1 through 5-HT7, show a regional distribution in brain areas involved in learning and memory, such as hippocampal formation (HF), amygdala and cortex. Although 5-HT7 receptor biological functions are still to be clarified, it was recently suggested that it may play a role in the control of learning and memory processes. The aim of our study was to assess the role of 5-HT7 receptors antagonist SB-269970 on working and reference memory in a radial arm maze task, utilizing a two-phase procedure, comprising an acquisition and test phase, conducted to evaluate working and reference memory, respectively. Our results showed that 5-HT7 receptors antagonist SB-269970 improved memory, decreasing the number of errors in test phase and, thus, affecting reference memory, while no effects were observed in working memory. These results could be explained taking into consideration the specific localization of 5-HT7 receptors in the CNS. In fact, high concentrations of 5-HT7 receptors were found in the HF, which exerts an important role on reference memory, while relatively low concentrations were present in the prefrontal cortex, involved in working memory. Thus, 5-HT7 receptor blockade had procognitive effect, when the learning task implicated a high degree of difficulty. This conclusion has a major implication in the context that 5-HT receptors play an important role under amnesia states (e.g., Alzheimer's disease) or when the learning is complex. (C) 2008 Elsevier B.V. All rights reserved.