Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism
Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism
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DOI：
10.1007/s00213-004-2074-5
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发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Cammarota, M
中科院分区：
文献类型：
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作者：
Kerr, DS;Bevilaqua, LRM;Cammarota, M
原理和目的：一些研究表明，大脑中的肾素-血管紧张素系统参与记忆巩固。然而，血管紧张素II（AII）在这一过程中的参与是有争议的。这可能是由于许多研究采用了多试验学习范式以及训练前脑室内输注来阐明这一问题，因此无法区分巩固和提取相关事件，并且缺乏解剖学特异性。为了解决这个问题，我们分析了AII在记忆巩固中所起的作用，使用了海马依赖的，一次试验，降压抑制回避任务（IA）结合立体定位的海马内药物输注。方法和结果：将输注套管双侧植入大鼠背侧海马（CA 1）的CA 1区，进行IA训练，24 h后测试记忆保持。我们发现，当立即或训练后30分钟（而不是更晚）注入CA 1时，AII产生剂量依赖性遗忘效应，而不改变运动活动、探索行为或焦虑状态。血管紧张素IV（AIV）不能模拟AII的遗忘作用，AII-2型受体（AT（2））拮抗剂PD 123319可完全阻断AII的遗忘作用，但AII-1型受体（AT（1））拮抗剂氯沙坦不能阻断AII的遗忘作用。重要的是，当单独输注时，PD 123319和氯沙坦都不会对记忆保持产生任何影响。结论：我们的数据表明，当给予CA 1时，AII通过激活AT（2）受体的机制阻断记忆的形成;然而，内源性AII似乎不参与IA长期记忆的巩固。
Rationale and objectives: Several studies suggest that the brain renin - angiotensin system is involved in memory consolidation. However, the participation of angiotensin II (AII) in this process is controversial. This is probably due to the fact that many of the studies carried out to elucidate this matter employed multitrial learning paradigms together with pretraining intracerebroventricular infusions, and therefore were unable to distinguish between consolidation and retrieval related events and lacked anatomical specificity. To circumvent this problem, we analyzed the role played in memory consolidation by AII using the hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Methods and results: Rats bilaterally implanted with infusion cannulae into the CA1 region of the dorsal hippocampus ( CA1) were trained in IA and tested for memory retention 24 h later. We found that when infused into CA1 immediately or 30 min after training but not later, AII produced a dose-dependent amnesic effect without altering locomotor activity, exploratory behavior or anxiety state. The amnesic effect of AII was not mimicked by angiotensin IV ( AIV) and was totally blocked by the AII-type 2 receptor ( AT(2)) antagonist, PD123319, but not by the AII- type 1 receptor (AT(1)) antagonist, losartan. Importantly, when infused alone, neither PD123319 nor losartan produced any effect on memory retention. Conclusions: Our data indicate that, when given into CA1, AII blocksmemory formation through a mechanism involving activation of AT(2) receptors; however, endogenous AII does not seem to participate in the consolidation of IA long-term memory.