Environmental enrichment exerts sex-specific effects on emotionality in C57BL/6J mice

Abstract

Environmental enrichment (EE) has been shown to exert various behavioral and mood effects in rodents including emotionality, which has a high propensity to be influenced by sex. However, there are only a few comparative studies evaluating the effect of EE and their results are both inconsistent and inconclusive. In the present study, male and female C57BL/6J adolescent mice were housed in either physical enrichment or standard conditions for four weeks with analysis of affective behaviors in the open field, elevated T-maze and forced swim tests. Hippocampal gene expression was characterized in an additional group of mice. In the open field test, exploration was similarly inhibited by EE in male and female mice. Both sex and housing condition influenced the time mice spent in the center of the arena. In the elevated T-maze, anxiety-like behavior was increased in female and decreased in male mice following EE. We observed a trend for EE-induced inhibition of glucocorticoid receptor (GR) mRNA expression in male but not in female mice. In contrast, mineralocorticoid receptor (MR) expression was unaffected by 10 days of physical enrichment but was lower in female mice compared to male mice. Our data suggest that the balance between hippocampal GR and MR may contribute to the observed sex-specific effect of physical enrichment on emotionality-related behavior.

Fig. 1

(a) Environmental enrichment housing. (b) Standard control housing. H, habitrail; R, running wheel; T, plastic toys.

Fig. 2

Mice performance in the open field test. (a) Distance traveled in the different regions of the open field and total distance traveled. (b) Interaction plot for total distance traveled. (c) Time spent in the center of the open field. (d) Interaction plot for time spent in the center zone. (e) Ratio of distance traveled in the center zone of the open field. (f) Interaction plot for center to total distance ratio. All data are presented as mean ± standard error of the mean (S.E.M).

Fig. 3

Mice performance in the elevated T-maze test. (a) Latency to enter the open arms. (b) Interaction plot for latency to enter the open arms. (c) Number of entries made into the open arms. (d) Interaction plot for open arm entries. (e) Time spent in the open arms. (f) Interaction plot for open arm time. All data are presented as mean ± S.E.M. * P < 0.05, ** P < 0.01.

Fig. 4

Mice performance in the forced swim test. (a) Latency to immobility. (b) Interaction plot for latency to immobility. (c) Total immobility time. All data are presented as mean ± S.E.M.

Fig. 5

(a) Hippocampal mRNA expression 10 days after differential housing. Data are presented as fold change over the mean value of male standard housing control group. All data are presented as means ± S.E.M. (b) Interaction plot for C-fos mRNA expression. Housing effect, P = 0.001; Sex effect, P < 0.05. (c) Interaction plot for Nr3c1 mRNA expression. (d) Interaction plot for Nr3c2 mRNA expression. Sex effect, P < 0.05.