Maternal Corticosterone Exposure and Enhanced Care in a Mouse Model of Childhood Adversity

Various rodent paradigms have been developed to study early-life adversity and stress-related changes in maternal care, but many rely on external stress procedures or disruption of the dam-pup environment. Moderate maternal corticosterone (CORT) exposure has instead been associated with heterogeneous offspring outcomes, ranging from vulnerability to resilience. Because maternal care may contribute to this variability, this protocol preserves the dam-pup unit while allowing maternal CORT exposure and sensitive caregiving to be studied experimentally. Particular attention is given to licking/grooming behavior, a form of sensitive maternal care associated with favorable developmental outcomes. Lactating C57BL/6 dams received 35 mg/L CORT in drinking water from postnatal day (PND) 0 to PND 21. Maternal care can additionally be enhanced by introducing a second female caregiver, creating distinct rearing conditions with increased opportunities for licking/grooming. Litter size was standardized on PND 5, and pups that were removed were used for the terminal collection of stomach milk to estimate offspring CORT exposure through lactation. Maternal care was observed on PND 2, 5, 8, 11, 14, and 17, including nest attendance, anogenital and body licking, different nursing postures, and spontaneous pup retrieval, as well as a pup retrieval test. Alternatively, a less intensive four-day observation schedule was evaluated, but produced less robust results. Maternal blood samples were collected to assess the acute and chronic effects of CORT ingestion. Together, these procedures provide a practical framework for studying how maternal CORT exposure and sensitive caregiving may jointly contribute to vulnerable or resilient developmental outcomes following early-life adversity.