Apelin receptor antagonist (ML221) facilitates memory reconsolidation in novel object recognition task

The apelin receptor (APJ), a G protein-coupled receptor, has recently attracted attention as a potential modulator of memory processes, largely through the activity of its endogenous ligand, apelin. However, the effects of APJ blockade on memory, particularly in the process of reconsolidation, remain poorly understood. In this study, we investigated the role of the selective APJ antagonist 5-[(4-Nitrobenzoyl)oxy]-2-[(2-pyrimidinylthio)methyl]-4H-pyran-4-one (ML221) in modulating memory reconsolidation using the novel object recognition (NOR) paradigm. The NOR reconsolidation procedure consisted of three phases: sampling, reactivation, and test. We found that administration of ML221 immediately after reactivation enhanced memory performance in the NOR task at doses of 0.1 and 0.3 mg/kg, but not at 1 mg/kg. This facilitative effect was absent when ML221 (0.1 mg/kg) was administered 6 hours after reactivation. Furthermore, ML221 (0.1 mg/kg) delivered 24 h after the sample phase, in the absence of reactivation, had no effect on NOR performance. Importantly, none of the tested doses (0.1, 0.3, and 1 mg/kg) of ML221 altered general locomotor activity or exploratory behavior. In conclusion, these findings provide the first evidence that antagonism of APJ by ML221 enhances NOR memory reconsolidation.