W.M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, NY, USA.
Depress Anxiety. 2011 Mar;28(3):186-93. doi: 10.1002/da.20803.
Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear.
Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the β-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala.
A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the β-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory.
Postretrieval β-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories.
创伤后应激障碍（PTSD）与去甲肾上腺素能活性增强有关。动物和人类研究表明，去甲肾上腺素能刺激增强了恐惧学习的巩固。通过呈现习得的恐惧线索来检索已建立的记忆会触发再巩固过程，在此过程中，记忆可能会被更新、削弱或增强。我们之前报道过，杏仁核中的去甲肾上腺素能阻断会损害恐惧记忆的再巩固。在这里，我们研究了去甲肾上腺素能增强对习得恐惧的再巩固的影响。
我们在大鼠中使用听觉恐惧条件反射，测试了在记忆检索后，杏仁核内注射β-肾上腺素能受体激动剂异丙肾上腺素或拮抗剂普萘洛尔对杏仁核中条件恐惧的影响。
单次在记忆检索后，在杏仁核内注射异丙肾上腺素增强了由习得的恐惧刺激引起的恐惧记忆，并在 48 小时后损害了这种记忆的消退。在连续检索试验后，在杏仁核内注射β-肾上腺素能受体拮抗剂普萘洛尔阻断了异丙肾上腺素对恐惧记忆的增强作用。
在记忆检索后，杏仁核中的去甲肾上腺素能刺激增强了恐惧记忆的再巩固，使它们不易消退。因此，在检索恐惧记忆时增加去甲肾上腺素能可能有助于创伤性记忆的持续存在和严重程度。再巩固可能是理解 PTSD 病理学的有用工具，因此可能有助于开发新的和修改现有的创伤性记忆治疗方法。
