Journal article
Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic-pituitary-adrenal axis adaptations to repeated stress
Journal of comparative neurology (1911), Vol.523(18), pp.2769-2787
12/15/2015
DOI: 10.1002/cne.23815
PMCID: PMC4607561
PMID: 26010947
Abstract
Emotional stressors activate a stereotyped set of limbic forebrain cell groups implicated in constraining stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation by inhibiting hypophysiotropic neurons in the paraventricular hypothalamic nucleus (PVH). We previously identified a circumscribed, anterior part of the bed nuclei of the stria terminalis (aBST) that houses stress-sensitive, PVH-projecting, γ-aminobutyric acid (GABA)-ergic neurons as representing a site of convergence of stress-inhibitory influences originating from medial prefrontal and hippocampal cortices. Here we investigate whether exaggerated HPA axis responses associated with chronic variable stress (CVS; daily exposure to different stressors at unpredictable times over 14 days, followed by restraint stress on day 15) and diminished HPA output seen following repeated (14 days) restraint-stress exposure are associated with differential engagement of the limbic modulatory network. Relative to acutely restrained rats, animals subjected to CVS showed the expected increase (sensitization) in HPA responses and diminished levels of activation (Fos) of GABAergic neurons and glutamic acid decarboxylase (GAD) mRNA expression in the aBST. By contrast, repeated restraint stress produced habituation in HPA responses, maintained levels of activation of GABAergic neurons, and increased GAD expression in the aBST. aBST-projecting neurons in limbic sites implicated in HPA axis inhibition tended to show diminished activational responses in both repeated-stress paradigms, with the exception of the paraventricular thalamic nucleus, in which responsiveness was maintained in repeatedly restrained animals. The results are consistent with the view that differential engagement of HPA inhibitory mechanisms in the aBST may contribute to alterations in HPA axis responses to emotional stress in sensitization and habituation paradigms.
Details
- Title: Subtitle
- Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic-pituitary-adrenal axis adaptations to repeated stress
- Creators
- Jason J Radley - Department of Psychological and Brain Sciences and Neuroscience Program, University of Iowa, Iowa City, Iowa, 52242Paul E Sawchenko - Laboratory of Neuronal Structure and Function and The Clayton Medical Research Foundation, The Salk Institute for Biological Studies, La Jolla, California, 92037
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.523(18), pp.2769-2787
- DOI
- 10.1002/cne.23815
- PMID
- 26010947
- PMCID
- PMC4607561
- NLM abbreviation
- J Comp Neurol
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Publisher
- Wiley; United States
- Grant note
- P01 DK026741 / NIDDK NIH HHS\nR01 MH095972 / NIMH NIH HHS\nDK-26741 / NIDDK NIH HHS\nMH-095972 / NIMH NIH HHS
- Language
- English
- Date published
- 12/15/2015
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070345902771
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