Enhanced caging and experimental design. Enrichment items were placed in experimental cages depending on condition and included a cardboard nest box (A), shredded paper nesting material (B), polycarbonate tube (C) and running wheel (D). Cage contents were arranged as described in Materials and Methods, and as pictured (E-H). (E) Standard caging (484 cm2 surface area) lacking enrichment items was used to house Cntl animals. (F) Larger caging (980 cm2) was used for Calm animals and these cages contained a corner-fitting cardboard nest box, shredded nesting material and a polycarbonate tube. (G) Cntl Ex caging (484 cm2) was similar to Cntl, but included a running wheel. (H) Calm Ex caging was also larger (980 cm2) and contained a nest box, shredded nesting material, a polycarbonate tube and a running wheel. (I) Experimental timeline; 8-wk-old male BALB/c mice (n = 10 per group) acclimatized to the husbandry facility in standard caging for 14 d. Animals were randomized and placed in respective experimental cages (five per cage) for 70 d. EPM studies were carried out at d 42.