Assessment of behavioral, clinical, and histological outcomes in Sprague-Dawley rats housed in enriched colony cages versus conventional pair housing over 28 days (2025)

Shamsi, A., Niebl, P., Kalina, A. et al.

Abstract

The standardization of husbandry in animal studies for drug development aims to minimize variability and enhance inter-laboratory comparability. Rats are a commonly used species in such studies. This standardization yields housing conditions that do not reflect the natural environment of rats, raising animal welfare concerns and prompting discussions about whether such conditions might also influence physiological or behavioral outcomes, thereby potentially affecting the translatability of study results. In this study, we compared a two-level, enriched colony cage housing groups of ten Sprague-Dawley rats with conventional pair-housed Type IV cages over 28 days, asking whether social and physical complexity alters parameters relevant to early drug development and safety assessment. These included body weight, food and water intake, behavior (open field, elevated plus maze), hematology, clinical chemistry, blood gases, gross pathology, organ weights, histopathology, and IgG levels. Differences in key measures between housing conditions were minimal: Hematology showed time-restricted shifts. On study day 28, immunoglobulin G concentrations were higher in conventionally housed animals, though values were comparable and within the normal range. Behavioral tests revealed notable but limited differences between housing conditions, mainly involving locomotor activity. Clinical chemistry and blood gases were largely unchanged. Body weight, food and water intake, and pathology parameters were comparable. Together, these findings demonstrate that enriched colony housing can be implemented as a refinement strategy without compromising the integrity of key study endpoints relevant to early drug development and safety assessment.