Unraveling Maternal Grief in Rats: From Neuroendocrine Dynamics to Neuroplasticity and Behavioral Adaptations

The bond between a mother and her infant is widely recognized as one of the most powerful connections in mammals. However, the loss of a child can have devastating effects on parents, leading to immense distress and trauma. Unfortunately, our understanding of the impact of child loss on the maternal neurobiology remains limited. To address this knowledge gap, in my thesis I conducted three separate studies using different protocols of maternal separation in lactating Sprague-Dawley rats to investigate how offspring loss affects the mother’s brain and behavior. In the first study, rats were subjected to brief (BMS; 15 minutes) or long repeated maternal separation (LMS; 180 minutes) during the first postpartum week. LMS dams displayed higher levels of behavioral alterations, as shown by increased pup licking and grooming (LG), and decreased maternal motivation compared to BMS and non-separated control dams. Moreover, BMS mothers exhibited lower plasma CORT concentrations compared to control dams, and OXT-R binding in limbic brain regions was higher in LMS dams compared to BMS and control mothers. The second study focused on the immediate effects of the permanent offspring loss over the first postpartum week; rat mothers experienced 1-, 3-, or 6- days of total offspring loss. Following 1 day of separation, the mother’s neuronal activity increased in the limbic system resulting in a positive correlation between the prelimbic cortex and basolateral amygdala, while OXT-R binding was decreased in the central amygdala following up to 3 days of separation. While plasma CORT levels did not differ between groups either under basal conditions or following stressor exposure on any of the days, the mother’s passive stress-coping was significantly increased after 6-days of offspring loss. In the third study, I investigated the long-term impact of offspring loss on rat dams at molecular and behavioral levels compared to control lactating dams and Virgins. One day of motherhood experience followed by 19-days of offspring loss resulted in an increased OXT-R binding and a decreased dendritic spine density in limbic brain regions of separated mothers whereas the number of estrogen receptor α and calbindin cells were not altered. Moreover, separated dams’ CORT plasma concentrations were back the level of Virgins. Importantly, the increased emotionality after long-term offspring loss as tested in the forced swim test (FST) could be rescued by central blockade of corticotropin-releasing factor receptors, but not by oxytocin (OXT) infusion. This thesis provides novel insight into the neurobiology of maternal grief and explore potential therapeutic interventions, which can offer better support for individuals going through the painful experience of grief.