title: Dysregulated hypothalamic-pituitary-adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress.
abstract: Organisms react to environmental challenges by activating a coordinated set of brain-body responses known as the stress response. These physiological and behavioral countermeasures are, in large part, regulated by the neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis. Normal functioning of the HPA axis ensures that an organism responds appropriately to altered environmental demands, representing an essential system to promote survival. Over the past several decades, increasing evidence supports the hypothesis that disruption of the HPA axis can lead to dysregulated stress response phenotypes, exacting a physiological cost on the organism commonly referred to as allostatic load. Furthermore, it has been recognized that high allostatic load can contribute to increased vulnerability of the organism to further challenges. This observation leads to the notion that disrupted HPA function and resulting inappropriate responses to stressors may underlie many neuropsychiatric disorders, including depression and anxiety. In the present set of studies, we investigate the role of both the normally functioning and disrupted HPA axis in the endocrine, neural, and behavioral responses to acute stress. Using a model of non-invasive chronic corticosterone treatment in mice, we show that dysregulating the normal function of the HPA leads to a mismatch between the hormonal and neural response to acute stress, resulting in abnormal behavioral coping strategies. We believe this model can be leveraged to tease apart the mechanisms by which altered HPA function contributes to neurobehavioral dysregulation in response to acute stress.
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University , Pullman, WA , USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kinlein
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University , Pullman, WA , USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Wilson
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University , Pullman, WA , USA.
authors.forename: Ilia N
authors.initials: IN
authors.lastname: Karatsoreos
keywords: allostatic load; c-Fos; corticosterone; hippocampus; prefrontal cortex
references.citation: Neurobiol Aging. 1997 Jan-Feb;18(1):45-55
references.pmid: 8983032
references.citation: Neurosci Biobehav Rev. 2011 Oct;35(9):1805-20
references.pmid: 21396397
references.citation: Cereb Cortex. 2009 Oct;19(10):2479-84
references.pmid: 19193712
references.citation: Physiol Rev. 2007 Jul;87(3):873-904
references.pmid: 17615391
references.citation: Mol Psychiatry. 2011 Feb;16(2):156-70
references.pmid: 20458323
references.citation: Annu Rev Immunol. 2002;20:125-63
references.pmid: 11861600
references.citation: Trends Neurosci. 2008 Sep;31(9):464-8
references.pmid: 18675469
references.citation: Neuroscience. 2012 Mar 1;204:5-16
references.pmid: 22214537
references.citation: Mol Neurobiol. 2009 Oct;40(2):166-82
references.pmid: 19653136
references.citation: Brain Res. 2008 Jun 18;1215:1-10
references.pmid: 18485334
references.citation: Physiol Rev. 1992 Jul;72(3):825-52
references.pmid: 1320764
references.citation: Brain Res. 2002 Jul 12;943(2):216-23
references.pmid: 12101044
references.citation: Psychoneuroendocrinology. 2012 Jan;37(1):27-38
references.pmid: 21616602
references.citation: Curr Neuropharmacol. 2008 Sep;6(3):235-53
references.pmid: 19506723
references.citation: Cell. 2014 Jan 30;156(3):522-36
references.pmid: 24485458
references.citation: Biol Psychiatry. 2008 Feb 15;63(4):353-9
references.pmid: 17889834
references.citation: Behav Brain Res. 2006 Apr 3;168(2):280-8
references.pmid: 16386319
references.citation: Biol Psychiatry. 2008 May 1;63(9):847-51
references.pmid: 18005940
references.citation: J Endocrinol. 2008 May;197(2):189-204
references.pmid: 18434349
references.citation: J Neuroendocrinol. 2009 Nov;21(11):898-909
references.pmid: 19732290
references.citation: J Neuroendocrinol. 2004 Dec;16(12):970-9
references.pmid: 15667452
references.citation: Endocrinology. 1988 Apr;122(4):1343-8
references.pmid: 2831028
references.citation: Ann N Y Acad Sci. 1988;525:18-26
references.pmid: 3291664
references.citation: Psychoneuroendocrinology. 2005 Feb;30(2):162-78
references.pmid: 15471614
references.citation: Physiol Behav. 2002 Nov;77(2-3):327-32
references.pmid: 12419409
references.citation: F1000Prime Rep. 2013 May 01;5:13
references.pmid: 23710327
references.citation: Eur J Endocrinol. 2001 Mar;144(3):199-206
references.pmid: 11248736
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1214-24
references.pmid: 16226365
references.citation: Neuroscience. 2012 Mar 1;204:83-9
references.pmid: 21939741
references.citation: J Neurosci. 2014 Jan 8;34(2):363-72
references.pmid: 24403138
references.citation: Trends Neurosci. 1998 Jul;21(7):294-9
references.pmid: 9683321
references.citation: Med Sci Monit. 2003 Feb;9(2):RA35-9
references.pmid: 12601304
references.citation: Comp Med. 2012 Oct;62(5):348-60
references.pmid: 23114038
references.citation: Am J Psychiatry. 1999 Apr;156(4):585-8
references.pmid: 10200738
references.citation: Am J Psychiatry. 1997 May;154(5):624-9
references.pmid: 9137116
references.citation: Endocrinology. 2010 May;151(5):2117-27
references.pmid: 20211972
references.citation: Am J Psychiatry. 2000 Aug;157(8):1252-9
references.pmid: 10910787
references.citation: Neuroscience. 1995 Jan;64(2):477-505
references.pmid: 7700534
references.citation: Pharmacol Ther. 1995;68(2):297-42
references.pmid: 8719972
references.citation: Pharmacol Biochem Behav. 2012 Jan;100(3):440-50
references.pmid: 22024161
references.citation: Brain Res. 1996 Jan 8;706(1):137-44
references.pmid: 8720501
references.citation: Trends Neurosci. 1997 Feb;20(2):78-84
references.pmid: 9023876
references.citation: Stress. 2013 Sep;16(5):587-91
references.pmid: 23662914
references.citation: Behav Brain Res. 2001 Nov 1;125(1-2):127-32
references.pmid: 11682103
references.citation: J Psychiatr Res. 2006 Sep;40(6):550-67
references.pmid: 16214171
references.citation: N Engl J Med. 1998 Jan 15;338(3):171-9
references.pmid: 9428819
references.citation: Front Neuroendocrinol. 2003 Jul;24(3):151-80
references.pmid: 14596810
references.citation: J Neurosci. 2005 Aug 24;25(34):7792-800
references.pmid: 16120780
references.citation: J Neurosci. 2011 Jul 20;31(29):10506-15
references.pmid: 21775596
references.citation: Trends Cogn Sci. 2011 Dec;15(12):576-84
references.pmid: 22078931
references.citation: Neurosci Lett. 2006 Aug 7;403(3):239-43
references.pmid: 16797121
references.citation: Neuroendocrinology. 2007;85(4):199-206
references.pmid: 17505125
references.citation: Endocrinology. 1989 May;124(5):2144-52
references.pmid: 2539968
references.citation: Ann N Y Acad Sci. 1998 May 1;840:33-44
references.pmid: 9629234
references.citation: Horm Behav. 2006 Feb;49(2):197-205
references.pmid: 16083887
references.citation: Alcohol Res. 2012;34(4):468-83
references.pmid: 23584113
references.citation: Horm Behav. 2003 Jan;43(1):2-15
references.pmid: 12614627
references.citation: Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85
references.pmid: 18282566
references.citation: J Clin Invest. 1995 Jul;96(1):231-8
references.pmid: 7615792
references.citation: Biol Psychiatry. 2006 Jun 15;59(12):1208-18
references.pmid: 16458266
references.citation: Integr Comp Biol. 2002 Jul;42(3):541-51
references.pmid: 21708749
references.citation: Arch Intern Med. 1993 Sep 27;153(18):2093-101
references.pmid: 8379800
references.citation: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9406-11
references.pmid: 20439721
references.citation: Br J Pharmacol. 1995 Nov;116(5):2417-24
references.pmid: 8581278
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14075-9
references.pmid: 19666502
references.citation: Nat Rev Neurosci. 2011 Nov 30;13(1):22-37
references.pmid: 22127301