Li Huang, Ying Lu, Wan Fu, Shiqiao Kang, Yijie Fang, Chuli Xiao, Xudong Yu, Xinhong Yin, Zhiyong Xiao
The Brain Cognition and Brain Disease Branch, Pu Ai Medical School, Shaoyang University, 422000, Shaoyang, China.
The First Affiliated Hospital, Department of Neurology, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China.
Physiol Behav. 2024 Apr 1;277:114461. doi: 10.1016/j.physbeh.2024.114461. Epub 2024 Jan 10.
Esketamine, the right-handed optical isomer of racemic ketamine, is a rapidly acting antidepressant approved by the FDA for treatment-resistant depression in 2019. However, few studies have investigated esketamine's role in learning and memory, particularly in the context of memory reconsolidation. Herein, we evaluated esketamine's role in memory reconsolidation in 7-week-old male Institute of Cancer Research mice subjected to the novel object recognition (NOR) memory task. The NOR reconsolidation procedure comprised three phases: sampling, reactivation, and testing. Esketamine-enhanced NOR memory performance when injected into mice 0 h after reactivation rather than following a 6 h delay. Conversely, administering esketamine 24 h after sampling without reactivation did not enhance NOR memory performance. Notably, esketamine exhibited no discernible effects on nonspecific responses, such as locomotor activity and exploratory behavior. Furthermore, the α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor antagonist NBQX effectively blocked the esketamine-induced enhancement of memory reconsolidation. In conclusion, esketamine treatment markedly improves memory reconsolidation in NOR tasks, and this effect is linked to AMPA receptor activity.
艾氯胺酮是消旋氯胺酮的右旋光学异构体，是一种起效迅速的抗抑郁药，于2019年被美国食品药品监督管理局（FDA）批准用于治疗难治性抑郁症。然而，很少有研究调查艾氯胺酮在学习和记忆中的作用，特别是在记忆重新巩固的背景下。在此，我们评估了艾氯胺酮在7周龄雄性癌症研究所小鼠的新物体识别（NOR）记忆任务中对记忆重新巩固的作用。NOR重新巩固程序包括三个阶段：采样、重新激活和测试。在重新激活后0小时而非延迟6小时注射到小鼠体内时，艾氯胺酮增强了NOR记忆表现。相反，在采样后24小时且未重新激活的情况下给予艾氯胺酮并没有增强NOR记忆表现。值得注意的是，艾氯胺酮对非特异性反应，如运动活动和探索行为，没有明显影响。此外，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型受体拮抗剂NBQX有效地阻断了艾氯胺酮诱导的记忆重新巩固增强。总之，艾氯胺酮治疗显著改善了NOR任务中的记忆重新巩固，并且这种作用与AMPA受体活性有关。
