Protective effect of 5-HT1B receptor gene deletion on the age-related decline in spatial learning abilities in mice.

We previously observed that 5 months old serotonin 1B receptor knockout (5-HT1BKO) mice exhibited a facilitation of learning in a long-term spatial memory task in a water maze. In this study, we attempted to assess whether this effect might persist during aging. We compared the performances of young-adult (3 months old) and aged (22 months old) 5-HT1BKO and wild type (WT) mice in the same task. Young-adult and aged KO mice exhibited facilitated acquisition of the reference memory task as compared to their respective WT controls. Generally, the performance of aged KO was similar to that of young-adult WT on the parameters defining performance and motor (swim speed) aspects of the task. During probe trials, all mice presented a spatial selectivity, which was, however, less pronounced in aged than in young-adult WT. No such age-related effect was observed in KO mice. In a massed spatial learning task, aged KO and WT mice globally exhibited the same level of performance. Nevertheless, young-adult and aged KO mice were superior to their WT controls as concerns the working memory component of the task. The data suggest that 5-HT1BKO mice are more resistant than WT to age-related memory decline as concerns both reference/long-term and working/short-term spatial memory.