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 -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.

中文翻译：

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艾氯胺酮增强新物体识别任务中的记忆重新巩固

艾氯胺酮是外消旋氯胺酮的右旋光学异构体，是一种速效抗抑郁药，于 2019 年被 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，特别是在记忆重建方面。在此，我们评估了 esketamine 在接受新物体识别 (NOR) 记忆任务的 7 周大雄性癌症研究所小鼠记忆重建中的作用。 NOR 重组过程包括三个阶段：采样、重新激活和测试。当重新激活后 0 小时而不是延迟 6 小时注射到小鼠体内时，Esketamine 增强了 NOR 记忆性能。相反，采样后 24 小时施用艾氯胺酮而不重新激活并不会增强 NOR 记忆性能。值得注意的是，艾氯胺酮对非特异性反应（例如运动活动和探索行为）没有表现出明显的影响。此外，-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型受体拮抗剂NBQX有效阻断艾氯胺酮诱导的记忆再巩固增强。总之，艾氯胺酮治疗显着改善 NOR 任务中的记忆重建，这种效果与 AMPA 受体活性有关。