Modulation of 5-HT7 receptor: effect on object recognition performances in mice

Recent data suggest that 5-HT7 receptors (5-HT7R) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HT7R in episodic-like memory, mice were administered 5-carboxamidotryptamine (5-CT, a 5-HT1A/1B/1D/7R agonist) and/or SB-269970 (a selective 5-HT7R antagonist) immediately after the acquisition session of the novel object recognition test.

The object recognition test was performed in order to assess the effects of modulation of 5-HT7R during consolidation phase on episodic-like memory performances in mice. A protocol including 3 days of familiarisation to the apparatus has been realised in order to decrease the effect of novelty-induced arousal.

With a 2-h delay, SB-269970 (3 and 10 mg/kg, administered subcutaneously) impaired the discrimination of the novel object. With a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with 5-CT (1 mg/kg) showed a significant discrimination. This promnesic effect with a long delay is effectively mediated by 5-HT7R activation since it was blocked by SB-269970 (10 mg/kg), but not by WAY-100135 (10 mg/kg) or by GR-127935 (10 mg/kg).

These data suggest that 5-HT7R tonically modulates cognitive processes involved in consolidation performances in object recognition. Therefore, 5-HT7R could be a promising target to treat memory dysfunctions (especially episodically related deficits) related to normal or pathological ageing.