Long-term offspring loss in lactating rats: Neurobiological and emotional consequences in a novel animal model

The maternal bond is a vital social connection that supports the survival and well-being of both the caregiver and offspring. Disruption of this bond, particularly following offspring loss, can result in profound trauma with long-lasting consequences. While considerable research has focused on the impact of maternal separation on offspring development, the biological effects of offspring loss on the mother remain largely unexplored. In this study, we examined the long-term effects of offspring loss on neuroplasticity, the oxytocin (OXT) and corticotropin-releasing factor (CRF) systems, and stress-coping behaviors in Sprague-Dawley rat mothers. We compared mothers that experienced one day of motherhood followed by 19 days of offspring loss, mothers that were with their pups throughout the 20 days, and naive virgin rats.

Our results reveal that mothers who lost their pups expressed increased oxytocin receptor binding and decreased dendritic spine density in limbic brain regions, with no changes in estrogen receptor α or calbindin cells. Additionally, separated mothers showed increased passive stress-coping behaviors in the forced swim test and elevated plasma corticosterone levels. Remarkably, the passive stress-coping behavior was rescued by central CRF receptor blockade but not by oxytocin treatment, suggesting that the CRF system plays a key role in the grieving process following offspring loss, and highlights the suitability of the rat model for studying maternal grief. This research provides insights into the complex neurobiology of grief, and suggests potential directions for future studies.