Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala
Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala
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DOI：
10.1590/s0100-879x1997000800009
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发表时间：
1997-08-01
影响因子：
2.3
通讯作者：
Izquierdo, I
中科院分区：
文献类型：
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作者：
Bevilaqua, L;Ardenghi, P;Izquierdo, I
雄性Wistar大鼠采用0.4 ma足震进行单次降压抑制性回避训练。在训练后的不同时间（植入海马CA1区0、1.5、3、6和9小时，植入杏仁核0和3小时），这些动物接受微量输注SKF38393 （7.5 μ g/侧）、SCH23390 （0.5 μ g/侧）、去甲肾上腺素（0.3 μ g/侧）、替莫洛尔（0.3 μ g/侧）、8- ohdpat （2.5 μ g/侧）、nan190 （2.5 μ g/侧）、forskolin （0.5 μ g/侧）、KT5720 （0.5 μ g/侧）或8-Br-cAMP （1.25 μ g/侧）。大鼠在训练后24小时进行记忆保留测试。当在训练后0小时给予去甲肾上腺素到海马体时，去甲肾上腺素增强记忆，而KT5720则健忘。训练后1.5 h，所有治疗均无效。训练后3或6小时给予8-Br-cAMP， forskolin, SKF38393；去甲肾上腺素和NAN-190引起记忆促进，KT5720、SCH23390、替马洛尔和8-OH-DPAT引起逆行性遗忘。同样，在训练后9小时，所有治疗都无效。在训练后0小时，去甲肾上腺素进入杏仁核引起逆行促进。注入杏仁核的其他药物没有产生任何显著的影响。这些数据表明，在训练后3和6小时，cAMP/蛋白激酶a通路参与记忆巩固，并受D-1、β和5HT1A受体的调节。这与训练后cAMP水平增加以及大鼠海马蛋白激酶a活性和CREB-P水平双峰（在训练后0和3-6小时）相关。这些结果表明，海马体，而不是杏仁核，参与了大鼠的长期储存降压抑制性回避。
Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala), these animals received microinfusions of SKF38393 (7.5 mu g/side), SCH23390 (0.5 mu g/side), norepinephrine (0.3 mu g/side), timolol (0.3 mu g/side), 8-OH-DPAT (2.5 mu g/side), NAN-190 (2.5 mu g/side), forskolin (0.5 mu g/side), KT5720 (0.5 mu g/side) or 8-Br-cAMP (1.25 mu g/side). Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393; norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D-1, beta, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h) in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.