Endocrine Abstracts

The dampening of hypothalamic–pituitary–adrenal (HPA) axis responses to a repeated stress is termed HPA habituation. We investigated here the effects of two commonly used repeated restraint stress paradigms, in which rats are exposed either to 10 episodes of 0.5 h restraint or 5 episodes of 3 h restraint. We compared ACTH, corticosterone, and testosterone responses, as well as corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA levels within brain regions involved in HPA regulation and ACTH secretion. Relative to initial exposures, declines in HPA activation measured by endocrine ACTH and corticosterone responses were remarkably similar among paradigms following repeated exposures. Compared to nonstressed controls, CRH mRNA in the paraventricular nucleus of the hypothalamus remained unchanged, while AVP mRNA was increased following 3 h, but not 0.5 h repeated restraint. 3 h repeated restraint increased AVP mRNA in the bed nucleus of the stria terminalis (BST), and CRH mRNA was increased in the BST and central amygdala. 0.5 h repeated restraint increased AVP mRNA levels in the medial amygdala, with no changes in the BST and central amygdala. In summary, despite comparable reductions in HPA activation, CRH and AVP expression within limbic and hypothalamic HPA neurons were differentially affected by each paradigm. Thus, the pathways recruited for HPA habituation appear to be distinct between these paradigms. Testosterone could be key to the differential peptide response, at least with respect to AVP expression, considering the extreme sensitivity of this peptide to changes in gonadal status.