Serotonin 5-HT6 receptor blockade reverses the age-related deficits of recognition memory and working memory in mice

Studies have shown that the blockade of 5-HT6 receptors (5-HT6R) can improve memory processes and reverse age-related spatial episodic like memory deficits. Since normal aging in the human is associated with a decline in episodic and working memory, we assessed the effect of the 5-HT6R blockade (SB-271046) on recognition memory (object recognition task) (a component of episodic like memory) in parallel to working memory (spontaneous alternation task in the T-maze) performances in young, adult, aged and senescent mice. Deficits in consolidation of non spatial recognition memory that were observed in 17- and 21-month-old mice were found to be reversed by 5-HT6R blockade. Deficits in working memory performances were only apparent as late as at 25 months of age; again, these deficits were reversed by 5-HT6R blockade. This study revealed in the mouse that, as in humans, working memory is more lately altered than recognition memory during aging and that such memory deficits could be counteracted by the use of 5-HT6R antagonists.