Inhibitory Function of the Dorsomedial Hypothalamic Nucleus on the Hypothalamic–Pituitary–Adrenal Axis Response to an Emotional Stressor but not Immune Challenge

K Ebner,N Singewald,P Muigg

doi:10.1111/j.1365-2826.2012.02369.x

Abstract

Accumulating evidence implicates the dorsomedial hypothalamic nucleus (DMH) in the regulation of autonomic and neuroendocrine stress responses. However, although projections from the DMH to the paraventricular hypothalamic nucleus (PVN), which is the critical site of the neuroendocrine stress axis, have been described, the impact of DMH neurones in the modulation of hypothalamic-pituitary-adrenal (HPA) axis activation during stress is not fully understood. The present study aimed to investigate the role of the DMH in HPA axis responses to different types of stimuli. Male Sprague–Dawley rats fitted with a chronic jugular venous catheter were exposed to either an emotional stressor (elevated platform-exposure) or immune challenge (systemic interleukin-1β administration). Bilateral electrolytic lesions of the DMH disinhibited HPA axis responses to the emotional stressor, as indicated by higher plasma adrenocorticotrophic hormone levels during and after elevated platform exposure in lesioned animals compared to sham-lesioned controls. Moreover, DMH-lesioned animals showed increased neuronal activation in the PVN, as indicated by a higher c-Fos expression after elevated-platform exposure compared to controls. By contrast, DMH-lesions had no effects on HPA axis responses to immune challenge. Taken together, our data suggest an inhibitory role of DMH neurones on stress-induced HPA axis activation that is dependent upon the nature of the stimulus being important in response to an emotional stressor but not to immune challenge.

Highlights

The dorsomedial hypothalamic nucleus (DMH) has been identified as a structurally and functionally diverse integrative structure involved in the regulation of physiological and behavioural stress responses [1,2,3,4,5,6]
Our results show no difference in adrenocorticotrophic hormone (ACTH) levels of lesioned and sham-lesioned control rats
Because we established that DMH lesions alter ACTH responses to elevated platform exposure but not to IL-1b, we examined whether these different ACTH responses are associated by different neuronal activation levels in the paraventricular nucleus (PVN), the apex of HPA axis

Summary

Introduction

The dorsomedial hypothalamic nucleus (DMH) has been identified as a structurally and functionally diverse integrative structure involved in the regulation of physiological and behavioural stress responses [1,2,3,4,5,6]. Local microinjection of muscimol, a selective GABAA receptor agonist, attenuates stress-induced elevations of ACTH levels [22] and c-Fos expression in the PVN [23] These observations support a model that GABA acts locally within the DMH to inhibit excitatory output pathways mediating neuroendocrine stress responses [2]. The only two studies examining HPA axis activity following DMH lesions reveal no clear-cut picture because they were performed either only under basal conditions [29] or using specific challenging situations such as osmotic stress [30] None of these studies have examined the effects of DMH lesions on HPA axis function during emotional stressors. As a non-emotional stimulus that potentially activates the HPA axis [31,32], we used an immune challenge induced by a single systemic interleukin (IL)-1b administration

Methods

Results

Conclusion