Assessing the effect of compounds from plantar foot sweat, nesting material, and urine on social behavior in male mice, Mus musculus

Authors: BARABAS, AMANDA - Purdue University; SOINI, HELENA - Indiana University; NOVOTNY, MILOS - Indiana University; LUCAS, JEFFREY - Purdue University; ERASMUS, MARISA - Purdue University; Cheng, Heng Wei; PLAME, RUPERT - University Of Veterinary Medicine; GASKILL, BRIANNA - Purdue University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/24/2022
Publication Date: 11/2/2023
Citation: Barabas, A.J., Soini, H.A., Novotny, M.V., Lucas, J.R., Erasmus, M.A., Cheng, H., Palme, R., Gaskill, B.N. 2023. Assessing the effect of compounds from plantar foot sweat, nesting material, and urine on social behavior in male mice, Mus musculus. PLOS ONE. 17(11). https://doi.org/10.1371/journal.pone.0276844.
DOI: https://doi.org/10.1371/journal.pone.0276844

Interpretive Summary: Aggression among group housed male mice is one of the most common reasons for premature euthanasia and reduces preclinical research data validity and reproducibility. Enrichment, such as transferring a portion of the existing nest material, is commonly suggested to reduce home cage aggression. In this study, the treatments were randomly assigned across cages and administered by spraying each of four respective compound solutions on the cage’s nesting material. Data from this study confirms previous strain patterns in social behavior and further validates wound assessment as a measure of escalated aggression. The findings provide insights for scientists to develop management strategies to reduce aggressive injury in mice and to increase preclinical research data validity and reproducibility.

Technical Abstract: Home cage aggression causes poor welfare in male laboratory mice and reduces data quality. One of the few proven strategies to reduce aggression involves preserving used nesting material at cage change. Volatile organic compounds from the nesting material and several body fluids not only correlate with less home cage aggression, but with more affiliative allo-grooming behavior. To date, these compounds have not been tested for a direct influence on male mouse social behavior. This study aimed to determine if 4 previously identified volatile compounds impact home cage interactions. A factorial design was used with cages equally split between C57BL/6N and SJL male mice (N=40). Treatments were randomly assigned across cages and administered by spraying each respective compound solution on the cage’s nesting material. Treatments were refreshed after study day 3 and during cage change on day 7. Home cage social behavior was observed throughout the study week and immediately after cage change. Several hours after cage change, feces were collected from individual mice to measure corticosterone metabolites as an index of social stress. Wound severity was also assessed after euthanasia. Measures were analyzed with mixed models. Volatile treatments did not impact most study measures. For behavior, SJL mice performed more aggression and submission and B6 mice performed more allo-grooming. Wound severity was highest in the posterior region of both strains, and the middle back region of B6 mice. Posterior wounding also increased with more observed aggression. Corticosterone metabolites were higher in B6 mice and in mice with more wounding treated with 3,4-dimethyl-1,2-cyclopentanedione. This data confirms previous strain patterns in social behavior and further validates wound assessment as a measure of escalated aggression. The lack of observed treatment effects could be due to limitations in the compound administration procedure and/or the previous correlation study, which is further discussed.