Sensitivity to glucocorticoid-mediated fast-feedback regulation of the hypothalamic-pituitary-adrenal axis is dependent upon stressor specific neurocircuitry.

Unlabelled: Fos-protein immunoreactivity (Fos-IR) was used to identify neurocircuits potentially participating in the regulation of hypothalamic-pituitary-adrenal (HPA) axis sensitivity to glucocorticoid-mediated fast-feedback in rats exposed to the physical stressor, hemorrhage, or the psychological stressor, airpuff startle. Marked regional brain differences in the Fos-IR expression were observed in response to these stressors. Specifically, after hemorrhage, nuclear Fos-IR increased in the nucleus of the solitary tract and other brainstem regions known to regulate hemodynamic processes including the supraoptic nucleus, and the magnocellular division of hypothalamic paraventricular nucleus (PVN). In contrast, after airpuff startle Fos-IR increased in the dorsomedial and lateral hypothalamus as well as in the lateral septum. Thus, activation of brainstem neurocircuits predominated after hemorrhage whereas activation of forebrain neurocircuits predominated after airpuff startle. In other regions, the magnitude of stressor-induced Fos-IR expression varied in a region-specific manner. When stressor exposure was preceded by administration of corticosterone to achieve levels within the physiological range after stressors, HPA axis responses were suppressed in response to the airpuff startle but not to either a small or moderate hemorrhage.

In Conclusion: (1) fast-feedback mediated inhibition of HPA axis activity is critically dependent upon stressor modality; (2) this apparent selectivity is reflected by differences in the nature of the neurocircuitry mediating these stressors. It is suggested that determination of the central actions of glucocorticoids in mediating fast-feedback regulation of the HPA axis requires evaluation of the interactions between activated glucocorticoid receptors and intracellular signaling cascades evoked by convergent neuronal input.