Effect of the calcium channel blocker amlodipine on memory in mice

David Quartermain, Allison Hawxhurst, Brandon Ermita, Jorge Puente
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引用次数: 25

Abstract

Five experiments were performed to investigate the effects of amlodipine, a calcium channel antagonist of the 1,4-dihydropyridine class, on consolidation and retrieval of memory in mice. In a single-trial passive avoidance task, amlodipine was administered pretraining, post-training, or pretesting. Results of temporal and dose—response studies showed that memory enhancement (significant increase in step-through latency) occurred when amlodipine (5, 7, 9, 15, and 30 mg/kg) was given either immediately post-training or (15 mg/kg) 15 min pretesting. Using a conditioned emotional response task, tone was paired with shock using Pavlovian conditioning procedures. Strength of conditioning was assessed by measuring suppression of drinking in the presence of a tone. Amlodipine (7 mg/kg) given immediately following both high- and low-intensity shock significantly enhanced conditioned suppression. In the third experiment thirsty mice were trained on a spatial discrimination task in a linear maze. Correct choices were reinforced with liquid reinforcement. Amlodipine (10 mg/kg) injected immediately after the training session produced a significant enhancement of discrimination performance on a 24-h retention test. In the fourth experiment mice were given 25 training trials in a two-way active avoidance task and were treated with either amlodipine (10 mg/kg) or saline after training. Amlodipine-treated mice made significantly more avoidances on the test session than control animals. The final experiment demonstrated that the deficit in approach-avoidance behavior seen in 18-month-old mice could be reversed by amlodipine treatment after the training session. These studies suggest that amlodipine can facilitate memory consolidation and retrieval.

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钙通道阻滞剂氨氯地平对小鼠记忆的影响
采用5项实验研究了1,4-二氢吡啶类钙通道拮抗剂氨氯地平对小鼠记忆巩固和恢复的影响。在单试验被动回避任务中,氨氯地平被用于训练前、训练后或测试前。时间和剂量反应研究结果表明,在训练后立即给予氨氯地平(5、7、9、15和30 mg/kg)或在测试前15分钟给予(15 mg/kg)时,记忆增强(步过潜伏期显著增加)发生。使用条件情绪反应任务,使用巴甫洛夫条件反射程序将语气与震惊配对。调节的强度是通过测量在有音调的情况下饮酒的抑制程度来评估的。高强度和低强度休克后立即给予氨氯地平(7mg /kg)可显著增强条件抑制。在第三个实验中,口渴的小鼠在线性迷宫中接受空间辨别任务的训练。正确的选择用液体补强。训练后立即注射氨氯地平(10mg /kg)在24小时滞留测试中显著增强了识别性能。在实验四中,小鼠进行了25次双向主动回避任务训练,训练后分别给予氨氯地平(10 mg/kg)或生理盐水。服用氨氯地平的小鼠在测试过程中比对照组小鼠有更多的回避行为。最后的实验表明,18个月大的小鼠在训练后的氨氯地平治疗可以逆转趋近回避行为的缺陷。这些研究表明氨氯地平可以促进记忆巩固和检索。
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