Cai Wen-Hui, Blundell Jacqueline, Han Jie, Greene Robert W, Powell Craig M
Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
J Neurosci. 2006 Sep 13;26(37):9560-6. doi: 10.1523/JNEUROSCI.2397-06.2006.
Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.
巴甫洛夫恐惧条件反射为包括创伤后应激障碍在内的后天焦虑症提供了最佳的啮齿动物模型之一。在恐惧条件反射范式训练后注射多种药物会损害恐惧记忆的巩固。事实上，早期临床试验表明，在创伤事件后立即给予此类药物可能会降低人类患创伤后应激障碍的风险（皮特曼等人，2002年；瓦伊瓦等人，2003年）。这种治疗方法的使用受到难以治疗每一位有风险的患者以及难以预测哪些患者会经历慢性不良后果的限制。最近的临床试验表明，给予糖皮质激素可能对已确诊的创伤后应激障碍（埃尔尼等人，2004年）和特定恐惧症（索拉维亚等人，2006年）有有益影响。相反，已知训练后给予糖皮质激素会增强记忆巩固（麦高和鲁曾达尔，2002年；鲁曾达尔，2002年）。从临床角度来看，增强恐惧记忆或重新激活的恐惧记忆是不可取的。我们在此报告，当在情境恐惧记忆重新激活后立即给予糖皮质激素时，随后的回忆会显著减少。额外的实验支持这样的解释，即糖皮质激素不仅会减少恐惧记忆的提取，此外，还会增强恐惧记忆消退的巩固，而不是减少重新巩固。正如其他人（埃尔尼等人，2004年；谢林等人，2004年）所指出的，基于增强消退的机制，这些发现为人类已确诊的后天焦虑症的潜在治疗提供了一种啮齿动物模型。
