Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Cogn Affect Behav Neurosci. 2023 Oct;23(5):1374-1383. doi: 10.3758/s13415-023-01118-z. Epub 2023 Jul 7.
Posttraumatic stress disorder (PTSD), a disabling and chronic condition after exposure to an extreme traumatic event, affects approximately 8% of the population worldwide. However, the underlying mechanisms of PTSD are not clear. The ability to manage fear memories is critical for PTSD. Differences in stress responsiveness and coping strategies by age represent an important starting point for the understanding and prevention of PTSD. However, we do not know whether the ability to cope with fear memories is decreased in middle-aged mice. To investigate this, we compared fear memory extinction among different age groups of mice. We found that middle-aged mice exhibited impaired fear memory extinction, which was accompanied by sustained enhanced long-term potentiation (LTP) induction in the extinction process. Most interestingly, ketamine treatment restored the impaired fear memory extinction in middle-aged mice. Moreover, ketamine could ameliorate the increased LTP during the extinction process through a presynaptic mechanism. Altogether, our results indicated that middle-aged mice were unable to extinguish fear memories, which could be treated with ketamine via presynaptic-mediated synaptic plasticity in middle-aged mice, suggesting that ketamine administration may be a new strategy for the treatment of PTSD.
创伤后应激障碍（PTSD）是一种暴露于极端创伤事件后的致残性和慢性疾病，影响着全球约 8%的人口。然而，PTSD 的潜在机制尚不清楚。管理恐惧记忆的能力对于 PTSD 至关重要。年龄导致的应激反应和应对策略的差异是理解和预防 PTSD 的重要起点。然而，我们并不知道中年小鼠是否会降低应对恐惧记忆的能力。为了研究这一点，我们比较了不同年龄组小鼠的恐惧记忆消除情况。我们发现，中年小鼠表现出恐惧记忆消除受损，伴随着在消除过程中持续增强的长时程增强（LTP）诱导。最有趣的是，氯胺酮治疗恢复了中年小鼠受损的恐惧记忆消除。此外，氯胺酮可以通过突触前机制改善消除过程中的增加的 LTP。总之，我们的结果表明，中年小鼠无法消除恐惧记忆，而氯胺酮可以通过突触前介导的突触可塑性来治疗中年小鼠的这种记忆消除受损，这表明氯胺酮的给药可能是治疗 PTSD 的一种新策略。
