Esketamine enhances memory reconsolidation in the novel object recognition task

Area of Science:

• Neuroscience
• Pharmacology
• Cognitive Science

Background:

• Esketamine, an FDA-approved antidepressant, has shown rapid effects in treatment-resistant depression.
• Its role in learning and memory, specifically memory reconsolidation, remains under-investigated.
• Understanding esketamine's impact on memory processes is crucial for its broader therapeutic potential.

Purpose of the Study:

• To evaluate the effect of esketamine on memory reconsolidation using the novel object recognition (NOR) task in mice.
• To determine the optimal timing for esketamine administration to influence memory reconsolidation.
• To investigate the involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in esketamine's effects on memory.

Main Methods:

• Utilized a novel object recognition (NOR) memory task in 7-week-old male Institute of Cancer Research mice.
• Administered esketamine at different time points relative to memory reactivation (0 h vs. 6 h delay) and sampling (24 h without reactivation).
• Assessed the impact of esketamine on memory performance and measured locomotor activity to control for nonspecific effects. Investigated the role of AMPA receptors using the antagonist NBQX.

Main Results:

• Esketamine significantly enhanced NOR memory performance when administered 0 h after reactivation, but not after a 6 h delay.
• Administration of esketamine 24 h after sampling without reactivation did not improve memory performance.
• Esketamine did not affect locomotor activity or exploratory behavior, indicating specific effects on memory.
• The AMPA receptor antagonist NBQX blocked the memory-enhancing effects of esketamine.

Conclusions:

• Esketamine administration directly after memory reactivation markedly improves memory reconsolidation in the NOR task.
• The pro-mnemonic effect of esketamine is dependent on the timing of administration relative to memory reactivation.
• Esketamine's enhancement of memory reconsolidation is mediated through the activity of AMPA receptors.