Drugs acting upon the cyclic adenosine monophosphate protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala
Drugs acting upon the cyclic adenosine monophosphate protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala
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DOI：
10.1097/00008877-199708000-00006
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发表时间：
1997-08-01
影响因子：
1.6
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
在背侧海马 CA1 区或杏仁核中两侧植入插管的大鼠，使用 0.4 mA 足部电击进行单次降压抑制（被动）回避训练。在训练后的不同时间（植入海马的动物为0、1.5、3、6或9小时；植入杏仁核的动物为0或3小时），他们接受8-Br-cAMP（环磷酸腺苷）（1.25μg/侧）、SKF38393（7.5μg/侧）、SCH23390（0.5μg/侧）的输注。 g/侧）、去甲肾上腺素ClH（0.3μg/侧）、噻吗洛尔ClH（0.3μg/侧）、8-HO-DPAT（2.5μg/侧）、NAN-190（2.5μg/侧）、毛喉素（0.5μg/侧）或KT5720（0.5μg/侧）。训练后 24 小时测试大鼠的记忆力。 SKF38393 是多巴胺 D-1 受体的激动剂，SCH23390 是多巴胺 D-1 受体的拮抗剂，噻吗洛尔是 β-肾上腺素受体拮抗剂，8-HO-DPAT 是 5HT(1A) 受体的激动剂，NAN-190 是 5HT(1A) 受体的拮抗剂，forskolin 增强腺苷酸环化酶，KT5720 抑制蛋白激酶 A。当给予海马 0 h 时训练后，去甲肾上腺素增强记忆力，KT5720 被遗忘。训练后 1.5 小时给予时，所有治疗均无效。训练后 3 或 6 小时给予 8-Br-cAMP、毛喉素、SKF 38393、去甲肾上腺素和 NAN-190 会导致记忆促进，KT5720、SCH23390、噻吗洛尔和 8-HO-DPAT 会导致逆行性遗忘。训练后 9 小时，所有治疗再次无效。当训练后 0 或 3 小时给予杏仁核时，除了 0 小时的去甲肾上腺素会导致逆行促进外，所有治疗均无效。这些数据与以下建议一致：在海马体中，而不是在杏仁核中，cAMP/蛋白激酶 A 通路参与训练后 3 小时和 6 小时的记忆巩固，并且这受到 D-1、β 和 5HT(1A) 受体的调节。这与之前的报告相关，即在该任务中大鼠海马体训练 3-6 小时后 cAMP 水平、蛋白激酶 A 活性和 P-CREB 水平增加。这可能表明海马体而不是杏仁核参与了大鼠降压抑制性回避的长期储存。
Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 mu g/side), SKF38393 (7.5 mu g/side), SCH23390 (0.5 mu g/side), norepinephrine ClH (0.3 mu g/side), timolol ClH (0.3 mu g/side), 8-HO-DPAT (2.5 mu g/side), NAN-190 (2.5 mu g/side), forskolin (0.5 mu g/side) or KT5720 (0.5 mu g/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D-1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT(1A) receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and 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, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D-1,beta, and 5HT(1A) receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.