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Front Psychiatry. 2015 Mar 13;6:31. doi: 10.3389/fpsyt.2015.00031. eCollection 2015.

Dysregulated hypothalamic-pituitary-adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress.

Frontiers in psychiatry

Scott A Kinlein, Christopher D Wilson, Ilia N Karatsoreos

Affiliations

  1. Department of Integrative Physiology and Neuroscience, Washington State University , Pullman, WA , USA.

PMID: 25821436 PMCID: PMC4358064 DOI: 10.3389/fpsyt.2015.00031

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.

Keywords: allostatic load; c-Fos; corticosterone; hippocampus; prefrontal cortex

References

  1. Neurobiol Aging. 1997 Jan-Feb;18(1):45-55 - PubMed
  2. Neurosci Biobehav Rev. 2011 Oct;35(9):1805-20 - PubMed
  3. Cereb Cortex. 2009 Oct;19(10):2479-84 - PubMed
  4. Physiol Rev. 2007 Jul;87(3):873-904 - PubMed
  5. Mol Psychiatry. 2011 Feb;16(2):156-70 - PubMed
  6. Annu Rev Immunol. 2002;20:125-63 - PubMed
  7. Trends Neurosci. 2008 Sep;31(9):464-8 - PubMed
  8. Neuroscience. 2012 Mar 1;204:5-16 - PubMed
  9. Mol Neurobiol. 2009 Oct;40(2):166-82 - PubMed
  10. Brain Res. 2008 Jun 18;1215:1-10 - PubMed
  11. Physiol Rev. 1992 Jul;72(3):825-52 - PubMed
  12. Brain Res. 2002 Jul 12;943(2):216-23 - PubMed
  13. Psychoneuroendocrinology. 2012 Jan;37(1):27-38 - PubMed
  14. Curr Neuropharmacol. 2008 Sep;6(3):235-53 - PubMed
  15. Cell. 2014 Jan 30;156(3):522-36 - PubMed
  16. Biol Psychiatry. 2008 Feb 15;63(4):353-9 - PubMed
  17. Behav Brain Res. 2006 Apr 3;168(2):280-8 - PubMed
  18. Biol Psychiatry. 2008 May 1;63(9):847-51 - PubMed
  19. J Endocrinol. 2008 May;197(2):189-204 - PubMed
  20. J Neuroendocrinol. 2009 Nov;21(11):898-909 - PubMed
  21. J Neuroendocrinol. 2004 Dec;16(12):970-9 - PubMed
  22. Endocrinology. 1988 Apr;122(4):1343-8 - PubMed
  23. Ann N Y Acad Sci. 1988;525:18-26 - PubMed
  24. Psychoneuroendocrinology. 2005 Feb;30(2):162-78 - PubMed
  25. Physiol Behav. 2002 Nov;77(2-3):327-32 - PubMed
  26. F1000Prime Rep. 2013 May 01;5:13 - PubMed
  27. Eur J Endocrinol. 2001 Mar;144(3):199-206 - PubMed
  28. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1214-24 - PubMed
  29. Neuroscience. 2012 Mar 1;204:83-9 - PubMed
  30. J Neurosci. 2014 Jan 8;34(2):363-72 - PubMed
  31. Trends Neurosci. 1998 Jul;21(7):294-9 - PubMed
  32. Med Sci Monit. 2003 Feb;9(2):RA35-9 - PubMed
  33. Comp Med. 2012 Oct;62(5):348-60 - PubMed
  34. Am J Psychiatry. 1999 Apr;156(4):585-8 - PubMed
  35. Am J Psychiatry. 1997 May;154(5):624-9 - PubMed
  36. Endocrinology. 2010 May;151(5):2117-27 - PubMed
  37. Am J Psychiatry. 2000 Aug;157(8):1252-9 - PubMed
  38. Neuroscience. 1995 Jan;64(2):477-505 - PubMed
  39. Pharmacol Ther. 1995;68(2):297-42 - PubMed
  40. Pharmacol Biochem Behav. 2012 Jan;100(3):440-50 - PubMed
  41. Brain Res. 1996 Jan 8;706(1):137-44 - PubMed
  42. Trends Neurosci. 1997 Feb;20(2):78-84 - PubMed
  43. Stress. 2013 Sep;16(5):587-91 - PubMed
  44. Behav Brain Res. 2001 Nov 1;125(1-2):127-32 - PubMed
  45. J Psychiatr Res. 2006 Sep;40(6):550-67 - PubMed
  46. N Engl J Med. 1998 Jan 15;338(3):171-9 - PubMed
  47. Front Neuroendocrinol. 2003 Jul;24(3):151-80 - PubMed
  48. J Neurosci. 2005 Aug 24;25(34):7792-800 - PubMed
  49. J Neurosci. 2011 Jul 20;31(29):10506-15 - PubMed
  50. Trends Cogn Sci. 2011 Dec;15(12):576-84 - PubMed
  51. Neurosci Lett. 2006 Aug 7;403(3):239-43 - PubMed
  52. Neuroendocrinology. 2007;85(4):199-206 - PubMed
  53. Endocrinology. 1989 May;124(5):2144-52 - PubMed
  54. Ann N Y Acad Sci. 1998 May 1;840:33-44 - PubMed
  55. Horm Behav. 2006 Feb;49(2):197-205 - PubMed
  56. Alcohol Res. 2012;34(4):468-83 - PubMed
  57. Horm Behav. 2003 Jan;43(1):2-15 - PubMed
  58. Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85 - PubMed
  59. J Clin Invest. 1995 Jul;96(1):231-8 - PubMed
  60. Biol Psychiatry. 2006 Jun 15;59(12):1208-18 - PubMed
  61. Integr Comp Biol. 2002 Jul;42(3):541-51 - PubMed
  62. Arch Intern Med. 1993 Sep 27;153(18):2093-101 - PubMed
  63. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9406-11 - PubMed
  64. Br J Pharmacol. 1995 Nov;116(5):2417-24 - PubMed
  65. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14075-9 - PubMed
  66. Nat Rev Neurosci. 2011 Nov 30;13(1):22-37 - PubMed

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