Memory facilitating effects of agomelatine in the novel object recognition memory paradigm in the rat

The aim of the present study was to evaluate the effects of agomelatine, an antidepressant with melatonergic agonist and 5-HT2C antagonist properties, in the rat novel object recognition (NOR) task, a model of short-term episodic memory. To assess the potential involvement of its chronobiotic activity, single intraperitoneal administration of agomelatine and NOR testing were performed either in the evening or in the morning. In both conditions, using a 24 h retention interval, vehicle-treated rats did not discriminate between the novel and the familiar object (recognition index was not different from chance performance) while object memory performance of rats treated with agomelatine either in the evening (10 and 40 mg/kg) or in the morning (2.5, 10, and 40 mg/kg) was significantly improved. Moreover, the selective 5-HT2C antagonist SB 242,084 (0.63, 2.5, and 10 mg/kg) and melatonin (2.5, 10, and 40 mg/kg) displayed also memory facilitating effects in both administration conditions. Finally, thioperamide used as positive reference compound to validate the experimental conditions, demonstrated a memory facilitating effect. In conclusion, agomelatine was shown to possess memory facilitating effects in the rat NOR task and both melatonergic agonist and 5-HT2C antagonist properties could be involved in these effects.

Research Highlights
► Agomelatine displays memory facilitating properties.
► Agomelatine improves memory performance in the NOR task in the rat.
► Melatonergic agonist and 5-HT2C antagonist properties are important for this effect.