LY294002, an inhibitor of phosphoinositide 3-kinase given into rat hippocampus impairs acquisition, consolidation and retrieval of memory for one-trial step-down inhibitory avoidance
LY294002, an inhibitor of phosphoinositide 3-kinase given into rat hippocampus impairs acquisition, consolidation and retrieval of memory for one-trial step-down inhibitory avoidance
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DOI：
10.1097/00008877-200112000-00007
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发表时间：
2001-12-01
影响因子：
1.6
通讯作者：
Izquierdo, I
中科院分区：
文献类型：
--
作者：
Barros, DM;Souza, TME;Izquierdo, I
成年雄性Wistar大鼠双侧背侧海马CAI区植入留置套管。一旦从手术中恢复，动物接受一次降压抑制性回避训练（3.0 s，0.4 mA足电击）。动物接受0.5-穆尔盐水或LY 294002（5、50或500 μ M）（磷酸肌醇3-激酶（PI 3-K）家族的抑制剂）的输注。在训练前10分钟、训练后立即或24小时保持测试前10分钟进行输注。在训练前和训练后组中，动物分别在训练后1.5和24小时进行两次测试，分别用于短期记忆（STM）和长期记忆（LTM）。训练前和训练后输注的药物抑制STM和LTM。试验前输注损害LTM回收。该效应不能归因于对运动、探索、促冲突或抗冲突行为的影响，因为LY 294002对高架十字迷宫行为没有影响。结果提示，海马PI 3-K对大鼠记忆的获得、巩固和对抑制性回避巩固的提取是必需的。这可能是由于与N-甲基-D-天冬氨酸（NMDA）受体复合物的相互作用或与细胞外调节蛋白激酶（ERK）-Ras信号通路的活性。(C)2001年利平科特威廉姆斯&威尔金斯。
Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the CAI region of the dorsal hippocampus. Once recovered from surgery, animals were submitted to one session of step-down inhibitory avoidance training (3.0 s, 0.4 mA footshock). Animals received a 0.5-mul infusion of saline, or of LY294002 (5, 50 or 500 muM), an inhibitor of the phosphoinositide 3-kinase (PI 3-K) family. Infusions were given 10 min before training, immediately post-training or 10 min prior to a 24-h retention test. In the pre- and post-training groups, the animals were tested twice: at 1.5 and 24 h after training, for short- (STM) and long-term memory (LTM), respectively. Pre- and post-training infusion of the drug inhibited both STM and LTM. Pre-test infusions impaired LTM retrieval. The effects can not be attributed to influences on locomotor, exploratory, pro- or anti-conflict behaviour, since LY294002 had no influence on elevated plus-maze behaviour. The results suggest that hippocampal PI 3-K is necessary for memory acquisition, consolidation and retrieval of the consolidation of step-down inhibitory avoidance in rats. This could be due to an interaction with the N-methyl-D-aspartate (NMDA) receptor complex or with activity of the extracellularly regulated protein kinase (ERK)-Ras signalling pathway. (C) 2001 Lippincott Williams & Wilkins.