Social Housing of Male CD-1 Mice (Mus musculus) in the Toxicological Setting: A 28-Day Social Compatibility Study of Male Mice following Oral Gavage of Theophylline

Group or pair housing of social animals in laboratory settings is beneficial to animal welfare. Social housing of male mice can be difficult due to possible aggressive behaviors, leading to injury and resulting in animals not being able to continue in the study. Techniques used to decrease male mouse aggression and territorial behaviors have been described in recent literature, including pairing mice before sexual maturity, moving used nesting material over during cage changes, removing high-value items that can encourage territorial behaviors, and using low-stress handling techniques. Using these suggested tactics, we conducted a 28-day study determining the social compatibility of male CD-1 mice in a standard toxicological study design. Forty-eight mice, aged 5 weeks old, were equally divided into single and pair housing and were administered theophylline daily. Animals were exposed to common toxicology study procedures known to cause additional stress including repeated blood collections, daily dosing, weekly clinical observations and body weights, and terminal urine collections. Behavioral assays, including nest scores and time-to-integrate-nest-material testing, were performed weekly, and pelt scores were collected postmortem. Fecal samples were collected intermittently for fecal corticosterone metabolite analyses. No mouse pairs required separation throughout the dosing phase of study, and no significant differences were observed that would affect toxicology studies. This suggests that by using techniques to decrease agonistic behaviors, male mice can be successfully socially housed on acute and subacute toxicology studies.