Early-life stressful experiences can have negative consequences on brain maturation. To understand the long-term implications of neonatal stress, researchers from Wayne State University’s Department of Psychology investigated the biobehavioral consequences of neonatal pain and maternal isolation in a rat model of neonatal stress. In a recent study by Mooney-Leber and Brummelte, rats underwent a series of stressful events during the first 4 days of life and were then assessed in a battery of behavioral and biomarker tests as adults to investigate changes in affective behaviors and HPA axis functionality. In the study, adult animals that underwent pain-related stress as neonates were assessed with behavioral tests including the open field test, novel object recognition test, Morris water maze, and restraint stress testing. HPA axis recovery in the adult subject was assessed by comparing serum corticosterone levels between stressed and non-stressed animals using an ELISA kit (K014-H1/H5) from Arbor Assays.

The authors found that early-life pain enhanced spatial learning independent of the animal’s sex, but altered HPA recovery from an acute stressor in females only. Moreover, reduced maternal care altered long-term spatial memory and reversal learning in males. The adult behavioral findings indicate that neonatal stressors have unique sex-dependent long-term biobehavioral effects in rodents. The observations suggest that stressors lead to adaptations in cognitive functioning that potentially favor learning at the cost of long-term memory. Pain-exposed female animals had significantly higher serum corticosterone 1 hr after stress exposure compared to non-pain-exposed females, while serum corticosterone levels in males were not significantly different between groups 1 hour after stress exposure.

The findings indicate that neonatal stressors have unique sex-dependent long-term biobehavioral effects in rodents and that females may be more vulnerable to the long-term consequences of early-life pain exposure. Continued examination of the behavioral consequences of these stressors may help explain varying vulnerability and resiliency in preterm infants who experienced early stress in the NICU. Further research characterizing additional behavioral domains and biological systems may ultimately aid in minimizing the consequences of early-life stress.