Sex-Specific Outcomes in a Rat Model of Early-Life Stress Due to Adverse Caregiving

Abstract

Early parental care is critical for the development of cortico-limbic circuits regulating stress responses and emotionalwell-being. Conversely, infant maltreatment can increase susceptibility to mood disorders—such as anxiety and depres-sion—and impair stress-coping abilities. Here, we employed the Scarcity-Adversity Model (SAM) in rats, limiting nestingresources from postnatal days 8–12, to examine its effects on maternal and adult offspring behavior. SAM-exposed moth-ers exhibited fragmented care and increased violence towards pups. By postpartum day (PPD) 13, maternal fecal corti-costerone metabolites (FCM) were elevated, indicating heightened stress. At weaning, SAM dams also showed increasedanxiety-like behavior in the Elevated Plus Maze (EPM), suggesting significant emotional alterations. In adulthood, SAM-exposed offspring underwent anxiogenic tests. Both male and female SAM offspring showed increased latency to enteropen arms and reduced risk-assessment in the EPM, though females displayed anxiolytic-like behavior in the Light-DarkBox. Male SAM rats had reduced locomotion in the Open Field, earlier onset and increased immobility in the ForcedSwim, and increased latency to groom in the Sucrose Splash. When exposed to acute stress, male SAM rats had lowerFCM levels, consistent with their passive stress reactivity. These findings confirm SAM induces long-lasting, sex-specificchanges in risk-taking, novelty responsiveness, and stress reactions, underscoring the importance of early nurturing inpromoting well-being and reducing psychopathological risk.