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Published on: June 13, 2021
Foster litters prevent hypothalamic-pituitary-adrenal axis sensitization mediated by neonatal maternal separation
R L Huot1, M E Gonzalez, C O Ladd
1Stress Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Insights
Neonatal maternal separation in rats increases stress responses, but providing foster litters during separation prevents these long-term effects, suggesting maternal care quality is key.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Endocrinology
Background:
- Neonatal maternal separation in rats is linked to long-term hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and anxiety.
- These effects may stem from disrupted maternal-pup interactions during the separation period.
Purpose of the Study:
- To investigate whether the quality of maternal care, rather than separation itself, mediates the long-term effects of neonatal maternal separation.
- To test if providing foster litters during separation mitigates the HPA axis and behavioral consequences.
Main Methods:
- Rat pups underwent daily maternal separation for 15 or 180 minutes from postnatal day 2-14.
- Mothers were either isolated or housed with foster litters during separation.
- Adult offspring were assessed for corticotropin-releasing factor (CRF) mRNA, stress reactivity, and HPA axis feedback.
Main Results:
- Long-term maternal separation (180 min) increased CRF mRNA, stress responses, and impaired HPA axis feedback.
- Rats exposed to separation with foster litters (HMS180F) showed intermediate CRF mRNA levels and normal stress/feedback regulation.
- Glucocorticoid receptor (GR) mRNA was elevated in the cortex of HMS180F rats.
Conclusions:
- The long-term adverse effects of neonatal maternal separation are significantly influenced by the quality of maternal care received.
- Altered maternal interactions, not just the separation experience, appear to drive lasting changes in the HPA axis and stress behavior.
- Foster litter exposure during separation protects against the detrimental long-term consequences of maternal separation.
Abstract:
Neonatal maternal separation of rat pups has been shown to produce long-term increases in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, elevated levels of hypothalamic corticotropin releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN), and enhanced anxiety-like behavior. These effects appear to be at least partially mediated by subtle disruptions in the quality of maternal-pup interactions. This hypothesis was tested by providing half the dams with foster litters during the maternal separation paradigm, so that in those litters, only the pups and not the dams were experiencing a period of separation. The separation protocol took place daily from PND2-14 for either 15 min (HMS15, handled) or 180 min (HMS180, maternal separation). During the period of separation dams were either transferred to adjacent cages without any pups present (HMS15, HMS180) or to cages containing an age-matched foster litter (HMS15F, HMS180F). As adults, the HMS180 progeny exhibited the expected increased expression of CRF mRNA in the PVN, stress hyper-responsiveness to airpuff startle and evidence of impaired feedback both in the CORT response, as well as in response to the dexamethasone suppression test. The HMS180F rats, however, appeared to be resistant to these effects of maternal separation as they demonstrated CRF mRNA levels intermediate between HMS15 and HMS180 rats. Their stress responses and feedback regulation of the HPA axis was comparable to that of the HMS15 rats. GR mRNA was elevated in the cortex of HMS180F rats. Overall, these studies support the thesis that the long-term effects of neonatal maternal separation may largely result from alterations in the quality of maternal care rather than from direct effects of the separation per se on the pups.
