The Dynamics of the Hypothalamic‐Pituitary‐Adrenal Axis During Maternal Deprivation

Abstract

A close contact between the dam and the litter is essential for the normal development of the hypothalamic-pituitary-adrenal (HPA) axis in rats and mice. Maternal signals, as licking and feeding, have been shown to sustain the HPA axis of the pups in a hypo-responsive state. Disruption of this mother-pup interaction by 24 h of maternal deprivation activates the otherwise quiescent stress system of the neonates, resulting in an enhanced adrenal sensitivity to adrenocorticotropic hormone (ACTH) and a decreased expression of central HPA markers, such as corticotropin-releasing hormone (CRH). However, the dynamics of these central and peripheral changes over the 24h period are largely unknown. In this study, we examined the time course of some of the central and peripheral indices of HPA activity during 24 h of maternal deprivation. We measured corticosterone and ACTH in the blood as well as CRH, mineralocorticoid and glucocorticoid receptor expression in the brain. Our results demonstrate that each of the components of the HPA axis responds to maternal deprivation at different time points following removal of the mother and with a very specific time course. The main activation of the HPA axis occurred between 4 h and 8 h of maternal absence. By contrast, during the second half of the deprivation period, negativefeedback mechanisms restrained the further increase in ACTH and corticosterone release. We conclude that maternal deprivation triggers a cascade of sequential changes at the various levels of the stress system, and that measuring only one aspect of the system at one time point does not accurately reflect the dynamic alterations of the HPA axis.

Neuropeptide Y mediates the initial hypothalamic–pituitary–adrenal response to maternal separation in the neonatal mouse

“…In contrast, we observed no effects of 8 h maternal separation on AVP expression in the PVN or GR expression in the CA1 region of the hippocampus. These data are in line with our previous findings, indicating that both transcripts change only in response to longer separation periods (Schmidt et al 2004). Taken together, it seems likely that the NPY-mediated activation of the HPA axis in the neonate mainly acts on CRH expressing neurons in the PVN.…”

“…We have previously shown that 8 h of separation are sufficient for a dramatic increase in plasma corticosterone as well as associated gene expression changes in the brain (Schmidt et al 2004). Further, these changes were accompanied (or even preceded) by alterations in peripheral metabolic signals as glucose or ghrelin.…”

Neonatal Isolation Stress Potentiates Cocaine Seeking Behavior in Adult Male and Female Rats

“…Numerous studies have investigated the effects of maternal separation on physiological changes, particularly with regard to HPA axis function. Results from these studies have shown that extended periods of separation (eg 24 h) were necessary to produce robust and enduring changes in HPA function (Schmidt et al, 2004;Levine, 2002;Rots et al, 1996). In contrast, McCormick et al (1998) reported that rats that were isolated from mother and siblings for only 1 h/day from postnatal day 2 through 9 showed increased plasma corticosterone levels, much higher than normal corticosterone levels in control animals.…”

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

“…It may, however, seem paradoxical that the CRH mRNA levels are suppressed rather than enhanced in these structures. However, it has been established that there is a robust modulation of key HPA axis molecules at different time points as the 24-h maternal deprivation progresses (Schmidt et al, 2004). The activation of the key elements of the HPA axis, namely CRH mRNA in PVN, plasma ACTH and corticosterone, occurs between 4 and 8 h of maternal absence.…”