Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze
Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze
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DOI：
10.1016/j.bbr.2012.12.014
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发表时间：
2013-03-15
影响因子：
2.7
通讯作者：
Savic, Miroslav M.
中科院分区：
文献类型：
--
作者：
Timic, Tamara;Joksimovic, Srdan;Savic, Miroslav M.
健忘症是苯二氮类药物中讨论最多的特性之一。苯二氮卓类药物对人类记忆的影响通常是顺行的，而逆行记忆功能的变化很少有报道。这种不一致的发现促使许多动物研究这些抑制性神经传递的正向调节剂对不同记忆阶段的影响。在苯二氮类药物中，咪达唑仑的记忆作用因其广泛而多样的临床应用而受到特别关注。成年雄性Wistar大鼠的Morris水迷宫实验分为三个实验，分别在每日学习前或学习结束后立即给予咪达唑仑0.5 mg/kg、1 mg/kg和2 mg/kg，每次实验一次，每次两次，然后进行探查试验。咪达唑仑即使在训练前剂量为0.5 mg/kg时，也会损害对隐藏平台位置的获得和随后的空间学习保持。这种低剂量与学习程序部分的损害无关，表现为在池的外围花费的时间增加。缺乏咪达唑仑对巩固的影响并没有被控制组观察到的低于机会的表现所混淆，因为我们在五次学习课程之后立即进行的使用安定的额外实验显示了类似的结果模式。最后，在探测测试前使用咪达唑仑会损害所有测试剂量下参考记忆的恢复。因此，在临床环境中使用咪达唑仑时，除了顺行性遗忘外，还应考虑到诱导逆行遗忘的可能性。(C)2012爱思唯尔B.V.保留所有权利。
Amnesia is one of the most discussed properties of the benzodiazepine class of drugs. The effects of benzodiazepines on human memory are usually anterograde, while changes in retrograde memory functions were seldom reported. Such inconsistent findings have prompted numerous animal studies investigating the influences of these positive modulators of inhibitory neurotransmission on different stages of memory. Among the benzodiazepines, memory effects of midazolam are of special interest due to its many and varied clinical applications. The present Morris water maze study in adult male Wistar rats was performed in three experiments in which midazolam was administered at doses of 0.5, 1 and 2 mg/kg intraperitoneally, before or immediately after each of five daily learning sessions, with two trials in a session, as well as before the probe test. Midazolam impaired acquisition and subsequent retention of spatial learning of the position of the hidden platform even at a pre-training dose of 0.5 mg/kg. This low dose was not associated with impairment of the procedural component of learning, manifested by increased time spent in the periphery of the pool. The lack of midazolam effect on consolidation has not been confounded by the observed below-chance performance of the control group since our additional experiment using diazepam also administered immediately after each of five learning sessions has revealed a similar pattern of results. Finally, midazolam administered before the probe test impaired retrieval of reference memory at all tested doses. Hence, induction of retrograde, besides anterograde amnesia should be kept in mind as a possibility when midazolam is used in clinical settings. (C) 2012 Elsevier B.V. All rights reserved.