Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome.

We have assessed the effects of enriched environment (EE) upon behavioral and cognitive performances of partially trisomic Ts65Dn (TS) mice and their control (CO) littermates. Enriched environment was applied to pups for 7 weeks after weaning. Circadian spontaneous activity (actimetry), exploratory behavior (hole board), activity in the open field and spatial memory (Morris Water Maze, repeated acquisition and cued paradigms) were analyzed in 86 female and 75 male mice, starting 15 days after completing enrichment. For each gender, mice were distributed in non-enriched and enriched control and trisomic groups. Enriched environment reduced in trisomic females and enhanced in trisomic males' circadian activity. Exploratory behavior was increased by enrichment in all groups, regardless of gender or presence of trisomy. In the Morris Water Maze, a significant improvement of the spatial memory was observed in enriched-control females, but not in enriched-control male mice, as assessed by distances traveled. Performances in the four groups of control animals were also consistently and significantly better than those of matching trisomic mice. In the acquisition trials, enrichment improved performance in trisomic female animals, but deteriorated in trisomic male mice. In all groups, changes in escape latencies and distances induced by enrichment were accounted for by changes in the total time spent in the periphery of the pool, indicating changes in learning strategy. Working memory was the function more affected by enrichment. It is concluded that enriched environment induces behavioral and learning changes in trisomic mice, although gender plays a significant modulatory role. Copyright 2002 Elsevier Science B.V.