Midazolam disrupts fear memory reconsolidation
Midazolam disrupts fear memory reconsolidation
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DOI：
10.1016/j.neuroscience.2005.12.064
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Molina, V. A.
中科院分区：
文献类型：
--
作者：
Bustos, S. G.;Maldonado, H.;Molina, V. A.
本研究以大鼠为实验对象，采用情境恐惧范式，通过3次情境电击训练实验（0.7 mA，3 s），考察了咪达唑仑（MDZ）对记忆再巩固的影响。首先，我们评估MDZ（lmg/kg，i. p.）在训练程序后不久注射。其次，我们检查了短暂暴露（90秒）后，无论是在训练环境（再激活程序）或在中性环境（无再激活程序）的MDZ的影响，一天后，冻结行为评分时，大鼠再次暴露于训练环境。第三，我们研究了在再激活后不同时间给予MDZ对恐惧记忆的影响以及再激活后10天这种影响的持续性。最后，我们测试是否MDZ效应可以通过一个单一的弱训练试验（0.2毫安，3秒）或由相同的非条件刺激的情况下，条件刺激作为一个提醒，这证明了诱导显着的冻结在大鼠以前没有训练的情况下，由介绍被逆转。结果表明，MDZ干扰形成的上下文恐惧记忆，只有当管理后的再激活程序，但不是训练程序后。这种干扰在重新激活后60分钟内有效，而在以后的时间内则无效。注射MDZ后11天，没有观察到冻结行为的自发恢复，弱训练试验和单独的非条件刺激都不能恢复冻结行为。所有这些数据都支持这样的观点，即通过MDZ刺激GABA A受体位点选择性地破坏背景恐惧记忆的再巩固过程。(c)2006由Elsevier Ltd代表IBRO出版。
The current research examines the influence of midazolam (MDZ) on memory reconsolidation using a contextual fear paradigm in rats, based on three context-shock training trials (0.7 mA, 3 s). First, we evaluate the effect of MDZ (1 mg/kg, i.p.) injected shortly after the training procedure. Second, we examined the influence of MDZ after a brief exposure (90 s) either in the training context (reactivation procedure) or in a neutral environment (no reactivation procedure) and one day later, freezing behavior was scored when rats were re-exposed to the training environment. Third, we investigate both the effect of MDZ administered at different times following reactivation on fear memory and the persistence of such effect 10 days after reactivation. Finally, we test whether the MDZ effect could be reverted by a single weak training trial (0.2 mA, 3 s) or by the presentation of the same unconditioned stimulus in the absence of the conditioned stimulus as a reminder which proves to induce significant freezing in rats not previously trained. Results show that MDZ interferes with the formation of a contextual fear memory only when administered after the reactivation procedure but not after the training procedure. This interference was effective up to 60 min after reactivation and not at a later time. No spontaneous recovery of freezing behavior was observed 11 days after MDZ injection which was not reverted by a weak training trial and by the unconditioned stimulus alone. All these data support the idea that stimulating GABA A receptor sites via MDZ selectively disrupts the reconsolidation process of a contextual fear memory. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.