ラメルテオンはマウスにおいて記憶の獲得を促進する

Abstract

Ramelteon, a synthetic and selective melatonin MT1/MT2 receptor agonist, tunes sleep-wake rhythms and is used for the treatment of insomnia. We previously reported that ramelteon modulated neocortical extracellular oscillations, suggesting the contribution of ramelteon on information processing in the brain. We supposed that ramelteon affects cognitive functions such as memory and learning and investigated whether ramelteon modulates the acquisition, consolidation, and/or retrieval of memory. To assess the effect of ramelteon on memory, we intraperitoneally injected saline or ramelteon (3mg/kg/day) into mice and conducted a novel object recognition test, in which two same objects were presented to freely moving mice in an open field on Day 1 (training session), and one object of the two was replaced with a novel object that had distinct color and shape on Day 2 (test session). To specify which phase (i.e., acquisition, consolidation, and/or retrieval) of memory was affected by ramelteon, we injected the drug 20 min before the training (acquisition group), immediately after the training (consolidation group), or 20 min prior to the probe test (retrieval group). We found that the discrimination performance for two distinct objects in the acquisition group was significantly higher in ramelteon-treated mice than saline-treated mice, but neither index for the consolidation nor retrieval group differed between ramelteon- and saline-treated mice. These results suggest that ramelteon specifically facilitates the acquisition phase of object recognition memory that possibly requires the perirhinal cortex and hippocampal CA1 area.