Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.
Max Planck School of Cognition, Leipzig, Germany.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Oct;7(10):970-978. doi: 10.1016/j.bpsc.2022.05.007. Epub 2022 May 30.
Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of posttraumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy, and preventing the dysregulations during exposure to threatening events may attenuate the development of PTSD symptomatology.
In a preregistered double-blind, between-subject, placebo-controlled pharmaco-functional magnetic resonance imaging design, this proof-of-concept study examined the potential of a single dose of the angiotensin II type 1 receptor antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n = 29) or placebo (n = 30) and a surprise memory test after a 24-hour washout.
LT generally improved memory performance and abolished emotional memory enhancement for negative but not positive material, while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. At the network level, LT reduced coupling between the hippocampus and the basolateral amygdala during successful memory formation of negative stimuli.
Our findings suggest that LT may have the potential to attenuate memory formation for negative but not positive information by decreasing hippocampus activity and its functional coupling strength with the amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD symptomatology.
过度兴奋和情绪记忆交互失调是创伤后应激障碍（PTSD）发展的关键病理失调。目前 PTSD 的治疗方法效果中等，在暴露于威胁性事件时预防失调可能会减轻 PTSD 症状的发展。
在一项预先注册的双盲、被试间、安慰剂对照的药物功能磁共振成像设计中，这项概念验证研究通过将情绪后续记忆范式与血管紧张素 II 型 1 受体拮抗剂氯沙坦（LT）或安慰剂（n=30）结合，并在 24 小时洗脱后进行惊喜记忆测试，检查单次服用 LT 减轻威胁性刺激的记忆优势和潜在神经机制的潜力。
LT 通常可以提高记忆表现，消除对负面但不是正面材料的情绪记忆增强，而编码期间的情绪体验仍然完整。LT 进一步抑制了随后记忆的负性刺激编码期间的海马体活动。在网络水平上，LT 降低了海马体和基底外侧杏仁核在成功记忆形成负性刺激时的耦合强度。
我们的研究结果表明，LT 可能通过降低海马体活动及其与杏仁核的功能耦合强度，从而减轻对负性但不是正性信息的记忆形成。这些发现表明，LT 有潜力预防负面事件的优先编码和记忆，这一机制可以预防 PTSD 症状发展的情绪记忆失调。
