A detailed characterization of loud noise stress: Intensity analysis of hypothalamo-pituitary-adrenocortical axis and brain activation

Abstract

The present studies were undertaken to help determine the putative neural circuits mediating activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and the release of adrenocorticotropin hormone (ACTH) and corticosterone in response to the perceived threat of loud noise. This experiment involved placing rats in acoustic chambers overnight to avoid any handling and context changes prior to noise exposure, which was done for 30 min (between 9:00 and 10:00 am) at intensities of 80, 85, 90, 95, 100, 105, and 110 dBA in different groups (n = 8), and included a background condition (60 dBA ambient noise). This manipulation produced a noise-intensity-related increase in plasma ACTH and corticosterone levels, with levels beginning to rise at approximately 85 dBA. c-fos mRNA induction was very low in the brains of the control and 80 dBA groups, but several brain regions displayed a noise-intensity-related induction. Of these, several forebrain regions displayed c-fos mRNA induction highly correlated (r > 0.70) with that observed in the paraventricular hypothalamic nucleus and plasma ACTH levels. These regions included the ventrolateral septum, the anteroventral subiculum, several preoptic nuclei, the anterior bed nucleus of the stria terminalis (BNST), the anterior paraventricular nucleus of the thalamus, and the medial subdivision of the medial geniculate body. Together with prior findings with audiogenic stress, the present results suggest that either or both the anterior BNST or the lateral septum is ideally situated to trigger HPA axis activation by stimuli that are potentially threatening.

Fig. 1

Mean levels of plasma corticosterone (μg/dl +SEM) and ACTH (pg/ml −SEM) following 30 min. of white noise presentation at intensities of 80, 85, 90, 95, 100, 105, or 110 dB (A scale, SPL). The 60 dBA group was not exposed to any noise presentation (ambient background noise). 85 dBA was the first intensity to evoke the release of plasma corticosterone and ACTH, and the levels of both hormones rose with increasing intensities, with the highest levels observed at 110 dBA.

Fig. 2

Representative photomicrographs of c-fos mRNA induction at different levels of the neuraxis for rats in the background noise condition (60 dB—far left column), 80 dB noise (middle left column), 95 dB (middle right column), and 110 dB (far right column). The different levels from top to bottom represent anterior to posterior brain sections. Note the increase in c-fos mRNA levels with increasing noise intensities in several brain regions. Abbreviations: AD, anterodorsal thalamic nucleus; AV, anteroventral thalamic nucleus; CG, cingulate cortex; BSTm, anteromedial bed nucleus of the stria terminalis; BSTv, anteroventral bed nucleus of the stria terminalis; IL, infralimbic cortex; Fl, flocculus; MGm, medial division of the medial geniculate body; MGv/d, ventral/dorsal divisions of the medial geniculate body; LHA, lateral hypothalamic area; LS, lateral septum; Orb, orbitofrontal cortex; Pir, piriform cortex; PVN, paraventricular nucleus of the hypothalamus; PVt, anterior paraventricular nucleus of the thalamus; SC, superior colliculus; SHy, septohypothalamic nucleus; SOC, superior olivary complex; Subv, anteroventral subiculum; Sum, supramammillary nucleus of the hypothalamus; Te, temporal (auditory) cortex; VCN, ventral cochlear nucleus.