Early vs. late maternal deprivation differentially alters the endocrine and hypothalamic responses to stress

Brain Res Dev Brain Res. 1998 Dec 7;111(2):245-52. doi: 10.1016/s0165-3806(98)00143-6.


Twenty-four hours of maternal deprivation results in persistent changes in the ACTH response to mild stress. These effects are dependent on the age of the neonate at the time of deprivation. Pups that were separated from the dam at postnatal days (pnd) 3-4 showed an enhanced stress-induced ACTH response at age 20, while pups deprived at pnd 11-12 displayed an attenuated ACTH response to stress at that time. The present study was designed to test the hypothesis that the immediate effects of deprivation at pnd 3 vs. pnd 11 would provide an explanation for these paradoxical effects observed at day 20. For this purpose, we measured the basal and the stress-induced ACTH and corticosterone (CORT) response at days 4 and 12, following 24 h of maternal deprivation. Furthermore, we examined whether similar differences in c-fos and CRH mRNA expression in the paraventricular nucleus (PVN) accompanied the differences in response characteristics of ACTH at pnd 20. The results indicate that changes in the ACTH and CORT responses were minimal after 24 h of maternal deprivation at day 4, whereas these hormones were markedly elevated following deprivation at day 12. The persistent effects also showed age-dependency: pups deprived early showed at pnd 20 an exaggerated ACTH response. Late deprived juveniles exhibited an attenuated ACTH response to stress at pnd 20 while in both conditions the CORT response was not different from the non-deprived litter mates. These persistent endocrine changes were accompanied by the changes in the neural stress markers. The expressions of c-fos and CRH mRNA in the PVN were at pnd 20 significantly greater in their controls in early-deprived animals. The late deprived juveniles showed a reduced response in these neural markers. In conclusion, the persistent alterations in ACTH are reflected by changes in c-fos and CRH mRNA, but these changes in endocrine and in neural stress markers do not appear to be related to any of the hormonal changes that occur at the time of maternal deprivation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Age Factors
  • Animals
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / genetics
  • Female
  • Gene Expression / physiology
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Maternal Deprivation*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Stress, Physiological / physiopathology*


  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone