Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran; Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):515-524. doi: 10.1016/j.pnpbp.2017.08.007. Epub 2017 Aug 8.
Glutamatergic and GABAergic systems play key roles in the hippocampus and affect the pathogenesis of anxiety- and memory-related processes. Some investigations have assessed the role of balancing the function of these two systems in different areas of the central nervous system (CNS) as an approach to manage the related disorders. We investigated the anxiety and avoidance memory states using the test-retest protocol in the elevated plus maze to understand the role of GABA receptors (GABARs) in relation to the NMDA receptor blockade by D-AP5 (an NMDA receptor antagonist). Also, we examined the function of Ca ions by blocking its entrance to the cell using SKF96365 (a Ca channel blocker). The drugs were injected into the CA3 region before the test. Our data showed that D-AP5 induced anxiolytic-like behaviors and impaired the avoidance memory. Injection of baclofen (a GABAR agonist), but not phaclofen (a GABAR antagonist) induced anxiolytic-like behaviors. Neither baclofen nor phaclofen altered avoidance memory-related behaviors. When baclofen was injected before D-AP5, it potentiated the anxiolytic-like behaviors induced by D-AP5, but counteracted its effect on avoidance memory. Phaclofen pretreatment attenuated D-AP5-induced anxiolytic-like behaviors, but potentiated its effect on avoidance memory. The effect of baclofen application before D-AP5 on anxiety and phaclofen application before D-AP5 on avoidance memory at the heist doses were accompanied by a decrease in locomotion. The application of SKF96365 did not alter anxiety-like behaviors but induced avoidance memory impairment. SKF96365 application before the combination of baclofen and D-AP5 counteracted the effects produced by the combination of baclofen and D-AP5 on anxiety and memory states. Our findings showed that the CA3 GABARs had a critical role in anxiolytic-like behaviors and avoidance memory deficit induced by D-AP5 and confirmed the role of Ca ions in the observed results.
谷氨酸能和 GABA 能系统在海马体中发挥关键作用，影响焦虑和记忆相关过程的发病机制。一些研究评估了平衡这两个系统在中枢神经系统（CNS）不同区域的功能的作用，作为管理相关疾病的一种方法。我们使用高架十字迷宫的测试-重测方案来研究焦虑和回避记忆状态，以了解 GABA 受体（GABARs）在与 NMDA 受体阻断剂 D-AP5（一种 NMDA 受体拮抗剂）相关方面的作用。此外，我们还通过使用 SKF96365（一种钙通道阻断剂）阻断钙离子进入细胞来检查钙离子的功能。药物在测试前注入 CA3 区域。我们的数据显示，D-AP5 诱导出焦虑样行为并损害回避记忆。注射巴氯芬（一种 GABAR 激动剂）而不是 phaclofen（一种 GABAR 拮抗剂）诱导出焦虑样行为。巴氯芬和 phaclofen 均未改变与回避记忆相关的行为。当巴氯芬在 D-AP5 之前注射时，它增强了 D-AP5 诱导的焦虑样行为，但抵消了其对回避记忆的作用。phaclofen 预处理减弱了 D-AP5 诱导的焦虑样行为，但增强了其对回避记忆的作用。在最高剂量下，D-AP5 之前应用巴氯芬对焦虑的影响和 D-AP5 之前应用 phaclofen 对回避记忆的影响伴随着运动减少。SKF96365 的应用不会改变焦虑样行为，但会导致回避记忆损伤。在巴氯芬和 D-AP5 组合之前应用 SKF96365 抵消了巴氯芬和 D-AP5 组合对焦虑和记忆状态产生的影响。我们的研究结果表明，CA3 GABARs 在 D-AP5 诱导的焦虑样行为和回避记忆缺陷中起关键作用，并证实了钙离子在观察到的结果中的作用。
