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Age-related impairment in fear memory extinction is restored by ketamine in middle-aged mice

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Abstract

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.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by Bethune Charitable Foundation (ezmr2002-002).

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Authors and Affiliations

  1. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Yingying Zhao, Hua Shao, Haitao Wang, Huijuan Li & Qiong Xue

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  1. Yingying Zhao
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Zhao, Y., Shao, H., Wang, H. et al. Age-related impairment in fear memory extinction is restored by ketamine in middle-aged mice. Cogn Affect Behav Neurosci 23, 1374–1383 (2023). https://doi.org/10.3758/s13415-023-01118-z

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