Bustos Silvia G, Maldonado Héctor, Molina Víctor A
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba, Argentina.
Neuropsychopharmacology. 2009 Jan;34(2):446-57. doi: 10.1038/npp.2008.75. Epub 2008 May 28.
Benzodiazepine (BDZ) administered shortly after retrieval disrupts the reconsolidation of fear memory. In this research, we explored the way in which different factors that limit the emergence of such process may affect BDZ's disruptive effect on fear memory reconsolidation. Animals were conditioned in a contextual fear paradigm; the consolidated memory was reactivated by exposure to the associated context for different periods of time that were followed by midazolam (MDZ) administration. We also studied MDZ amnesic effect after reactivating fear memories of several ages. We finally analyzed the effectiveness of different MDZ doses in preventing the reconsolidation of different age fear memories. The memory trace was disrupted following MDZ when the reactivation session lasted 3-5 min but it was not after a briefer 1-min reactivation period. Over a 10-min reactivation session, all animals gradually reduced their fear response, which indicates the emergence of the extinction process. When tested, MDZ rats exhibited a robust fear, suggesting that MDZ impaired the consolidation of extinction. In a 3-min reactivation session, MDZ (1-1.5 mg/kg) prevented the reconsolidation of recently acquired memories. A 21-day-old fear memory was only vulnerable to MDZ at a 1.5 mg/kg dose with a reactivation session of 5 and not 3 min, whereas a 36-day-old memory was only disrupted with a higher MDZ dose (3 mg/kg) regardless of the reactivation trial's duration. This study demonstrated MDZ's interference on fear-memory reconsolidation within a relatively short reactivation period in recently acquired memories. Over longer reexposure, MDZ disrupts the consolidation of extinction. A longer duration of the reexposure session, as well as higher MDZ doses, is required to prevent the reconsolidation process of remote fear memories.
在取回后不久给予苯二氮䓬（BDZ）会破坏恐惧记忆的重新巩固。在本研究中，我们探讨了限制该过程出现的不同因素可能影响BDZ对恐惧记忆重新巩固的破坏作用的方式。动物在情境恐惧范式中进行条件化训练；通过暴露于相关情境不同时间段来重新激活巩固的记忆，随后给予咪达唑仑（MDZ）。我们还研究了重新激活不同年龄恐惧记忆后MDZ的遗忘效应。我们最终分析了不同MDZ剂量在预防不同年龄恐惧记忆重新巩固方面的有效性。当重新激活期持续3 - 5分钟时，MDZ给药后记忆痕迹被破坏，但在较短的1分钟重新激活期后则未被破坏。在10分钟的重新激活期内，所有动物的恐惧反应逐渐降低，这表明消退过程的出现。测试时，MDZ处理的大鼠表现出强烈的恐惧，表明MDZ损害了消退的巩固。在3分钟的重新激活期内，MDZ（1 - 1.5毫克/千克）可预防近期获得的记忆的重新巩固。21天大的恐惧记忆仅在1.5毫克/千克剂量且重新激活期为5分钟而非3分钟时易受MDZ影响，而36天大的记忆无论重新激活试验的持续时间如何，仅在较高的MDZ剂量（3毫克/千克）下被破坏。本研究证明了MDZ在相对较短的重新激活期内对近期获得的记忆中恐惧记忆重新巩固的干扰作用。在更长时间的再次暴露中，MDZ会破坏消退的巩固。需要更长的再次暴露期以及更高的MDZ剂量来预防远期恐惧记忆的重新巩固过程。
