Rapamycin prevents, but does not rescue learning and memory deficits.

<p>(<b>A</b>) Mice were evaluated in the spatial reference version of the MWM. Mice significantly learned the task over the 5 days of training, as indicated by a reduced time to find the escape platform (F = 36.2; p<0.0001 as calculated by a mixed-model repeated-measures ANOVA). There was also a significant genotype/treatment-day interaction (F = 2.68; p = 0.021). Bonferroni post hoc analysis showed that the NonTg^2–18 mice learned the task significantly quicker than the NonTg^CTL mice. In contrast, the NonTg^15–18 mice learned as well as the NonTg^CTL mice. Similarly, 3 months of rapamycin treatment did not improve learning in the 3xTg-AD mice as the 3xTg-AD^15–18 mice performed similarly to the 3xTg-AD^CTL mice. In contrast, we found that the 3xTg-AD^2–18 mice learned the task significantly quicker than 3xTg-AD^CTL mice and as well as NonTg^CTL mice. (<b>B–C</b>) Reference memory, measured 24 hours after the last training trials was significantly improved only in the NonTg^2–18 and 3xTg-AD^2–18 mice compared to the NonTg^CTL and 3xTg-AD^CTL mice, respectively. Three months of rapamycin administration, however, did not have any effect on reference memory. (<b>D–E</b>) Swimming speed and distance traveled during the probe trials were not significantly different among the 6 groups of mice. (<b>F</b>) Mice were also tested using the object recognition task, a cortical-dependent task. One-way ANOVA showed significant changes in the time mice spent exploring the new object across the 6 different groups (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025416#pone-0025416-g002" target="_blank">Fig. 2F</a>; p = 0.01). Post-hoc analysis showed that short- and long-term rapamycin treatment had no effect on NonTg mice. In contrast, the 3xTg-AD^2–18 mice performed significantly better than the 3xTg-AD^CTL mice. Data are presented as means ± SEM.