Postweaning Development of Negative Feedback in the Pituitary-Adrenal System of the Rat

Abstract

In response to ether or electric shock, plasma corticosterone concentrations in weanling and adult rats rose to equivalent levels by 15 min, but then diverged, with the weanlings showing a later peak and a slower return to resting levels. An interpretation of this effect, in terms of an immature feedback mechanism in weanling rats, was supported by an experiment in which pretreatment with peripherally injected dexamethasone completely blocked a plasma corticosterone increase, in response to an ether and blood sampling stress in adults, but only partially reduced this response in weanlings. The failure of basal hypothalamic implants of corticoids to differentiate between ages in their ability to inhibit this stress response supported the suggestion of extra-hypothalamic inhibitory systems as the loci of the deficit in weanlings.

The adolescent brain and age-related behavioral manifestations

“…Based on the finding that adolescents with depression are less likely to exhibit hypercortisolism than depressed adults [441], Dorn and Chrousos [141] hypothesized that negative feedback loops within the HPA system may function better in adolescents than adults. This hypothesis is contrary to results obtained in animal studies where it appears that the delayed post-stress return to basal corticosterone levels seen in juvenile rats [202] may extend into the early-to mid-adolescent period [82,482]. This apparent prolongation of the stress-induced increase in corticosterone in adolescents relative to adults may reflect a variety of factors, including slower ACTH metabolism, delayed adrenal secretion of corticosterone, immature negative feedback regulation mediated at least in part by glucocorticoid receptors in hippocampus, or perhaps even transiently enhanced positive feedback.…”

“…Rodent studies have shown significant stressinduced activation of the HPA axis in neonatal rat pups, although sensitivity to stressors is reduced considerably after the first several postnatal days, with this stress hyporesponsive period (SHRP) lasting for most of the first 2 weeks of postnatal life [481]. While similar peak corticosterone responses to stressors have occasionally been observed in weanlings, adolescent and adult rats [23,82,202], stress-induced HPA activation has more consistently been reported to increase ontogenetically following the SHRP in rats to reach an asymptote around adolescence, at least in males [29,357,452,463,569,574]. In recent work using mice, however, adolescents were observed to have lower corticosterone levels than adults following the mild stress of saline injection [312].…”

Impact of Maternal Deprivation on Brain Corticotropin-Releasing Hormone Circuits: Prevention of CRH Receptor-2 mRNA Changes by Desipramine Treatment

“…This persistent elevation of CORT and ACTH is also seen in the NDEP animal once it exhibits an adrenocortical response to stress at 15 days of age (Suchecki et al, 1995). The inhibition of the adrenocortical stress response is achieved by 25 days of age when a more efficient ACTH inhibition and metabolic clearance is possible (Goldman et al, 1973;Vázquez, 1998;Vázquez and Akil, 1993;Vázquez et al, 1997). We found that NDEP and DEP animals treated with chronic isotonic saline injections had low CORT levels at 120 min, and that DES treatment resulted in a more efficient inhibition of the adrenocortical response by 60 min after the 3% saline challenge.…”

Prenatal stress does not alter innate novelty-seeking behavioral traits, but differentially affects individual differences in neuroendocrine stress responsivity

“…Several elegant studies have described the ontogeny of the rodent HPA axis, and specifically demonstrated that glucocorticoid suppression of the HPA axis remains immature and continues to develop during the postweaning period (21-25 days old) (Goldman et al, 1973, Sapolsky and Meaney, 1986, Vazquez et al, 1996. For instance, two studies showed that ether stress elicited a prolonged corticosterone response in 25 day-old pups, with near peak corticosterone levels persisting 60-min after stress exposure, unlike adult animals that showed a rapid inhibition of corticosterone secretion (Goldman et al, 1973, Vazquez et al, 1996. Our present results with HR weanlings (both PS and control groups), as well as the PS-LR weanlings resemble these findings, since all three groups show high, near peak corticosterone levels 60-min after exposure to the open field.…”