Morris Water Maze to evaluate the effect of age, ovariectomy, and genetic Fshr depletion in 3xTg females on acquisition of spatial memory. In 5–month–old sham–operated 3xTg mice (A), latency to find the hidden platform (seconds, s) was significantly shorter for 3xTg;Fshr−/− on days 3, 4 and 5 of the acquisition trials compared with 3xTg;Fshr+/+ mice. At 10 months (B), the effect was significant on days 4 and 5 in 3xTg;Fshr−/− mice and on day 5 in 3xTg;Fshr+/− mice. In ovariectomized mice, there was no difference between the groups at 5 months of age (C), but at 10 months (D), the 3xTg;Fshr−/− mice showed shorter latency compared with the 3xTg; Fshr+/− group at days 4 and a trend toward significance on days 3 and 5. Mice that showed repeated episodes of extensive floating (>10 s per trial or >25% of trial time across 5 days) were excluded from the analysis. N=10 to 14 mice per group; Mean ± SEM; P values as shown, significant at P≤0.05; repeated measures ANOVA followed by Fisher’s Least Significant Difference post–hoc analyses).