Hypophysiotropic neurons of the paraventricular nucleus respond in spatially, temporally, and phenotypically differentiated manners to acute vs. repeated restraint stress: Rapid publication

Abstract

Hypothalamic-pituitary-adrenal (HPA) responses to stress are initiated by parvicellular neurosecretory neurons in the medial parvicellular (mp) part of the paraventricular hypothalamic nucleus (PVH), which express corticotropin-releasing factor (CRF), among other neuropeptides. We have used an approach guided by patterns of stress-induced Fos expression to explore the manner in which anatomically and phenotypically defined components of the mpPVH respond to acute vs. repeated restraint stress. Hormonal indices of HPA activation in animals exposed to the last of 14 daily repeated restraint sessions were significantly lower than those in rats receiving a single restraint episode. Although this habituation was paralleled by global decrements in activation patterns across all PVH compartments, clear spatial-temporal differences in recruitment profiles were noted between dorsal and ventral aspects of the mpPVH. Thus, acute restraint provoked a biphasic Fos induction, which occurred first within the mpPVH and in an adjoining population of somatostatinergic cells in the periventricular region and only later within other aspects of the PVH. By contrast, Fos responses of habituated animals were monophasic and focused decisively within a discrete ventral aspect of the mpPVH. The ventral population was identified as comprising neurons that express CRF and/or enkephalin and, to a lesser extent, growth hormone-releasing factor. These results indicate a lack of homogeneity among stress-responsive parvicellular neurosecretory neurons and suggest that distinct complements of CRF cells may be preferentially involved in initiating HPA responses to acute stress and sustaining them in the repeated condition.

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

“…The suppression of corticosterone secretion following exposure to stress was accompanied by a reduction in neuronal activation of the mpdPVN of the hypothalamus, an area that contains all the CRH neurosecretory cells that regulate ACTH secretion through communication with the anterior pituitary. Although we did not assess CRH mRNA in this study, the region of interest we analyzed in the mpdPVN here is where all CRH neurosecretory cells are amassed (Viau and Sawchenko, 2002;Viau et al, 2005) suggesting that a suppression of stress-induced activation of CRH neurosecretory cells is likely mediating the effect of desipramine in this study. In support of this hypothesis, a recent report has demonstrated that reductions in stress-induced CRH transcription are associated with suppression of stressinduced peripheral corticosterone secretion following desipramine treatment (Conti et al, 2004).…”

“…Discrete localization of Fos-ir profiles to the dorsal medial parvocellular (neuroendocrine anterior pituitary regulating) population of the PVN (mpdPVN) was accomplished by limiting the region of interest to the area medial to the magnocellular population, lateral to the periventricular zone, and ventral to the dorsal cap, as has been carried out previously. This conservative analysis ensures that all slices are examined at the same rostral-caudal axis and also ensures that the region of interest is where all the CRH neurosecretory cells, which communicate to the anterior pituitary to stimulate ACTH, are amassed (Viau et al, 2005;Viau and Sawchenko, 2002). Cell number estimates were generated by counting bilaterally the number of Fospositive cells through the medial parvocellular cell population, averaged by dividing cell counts by slice number, and corrected for sampling frequency (one in five sections, 150-mm intervals) by multiplying this product by a factor of five.…”

The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic–pituitary–adrenocortical axis responsiveness to acute and chronic stress

“…In particular, chronic stress can lead to potentiated basal ACTH and/or corticosterone secretion, adrenal hypertrophy and elevated PVN CRH and AVP mRNA and protein expression (Hauger et al, 1988;Herman et al, 1995;Kiss and Aguilera, 1993;Ulrich-Lai et al, 2006b). Chronic exposure to homotypic stressors typically engender some degree of HPA axis habituation (Dhabhar et al, 1997;Odio and Brodish, 1989;Pitman et al, 1988;Viau and Sawchenko, 2002). However, despite the presence of an enhanced glucocorticoid feedback signals, HPA responses to new stressors are either maintained or augmented following chronic stress a process known as stress facilitation (Armario et al, 1985;Bhatnagar and Dallman, 1998;Bhatnagar and Vining, 2003;Dallman et al, 1992;Hauger et al, 1990;Kiss and Aguilera, 1993;Ostrander et al, 2006).…”

Corticotropin-releasing hormone receptors in the medial prefrontal cortex regulate hypothalamic–pituitary–adrenal activity and anxiety-related behavior regardless of prior stress experience

“…Rats in repeated stress groups were exposed to 8 consecutive days of 30 min restraint per day. We, and other groups, have observed habituation of ACTH and corticosterone responses following 30min of restraint per day for 8 days and up to14 days (Viau and Sawchenko, 2002;Jaferi et al, 2003;Jaferi & Bhatnagar, 2006).…”

“…Together, the evidence discussed above suggests that activity in the mPFC regulates both acute and repeated stress-induced HPA activity. Repeated exposure to the same, homotypic stressor can produce a gradual decrement, or habituation, of HPA activity (Bhatnagar & Meaney, 1995;Li & Sawchenko, 1998;Garcia et al, 2000;Viau and Sawchenko, 2002;Jaferi & Bhatnagar, 2006). Habituation to repeated stress may involve discrimination of the stressor as a familiar and previously encountered stressor as opposed to one that is novel.…”