title: Recovery from disrupted ultradian glucocorticoid rhythmicity reveals a dissociation between hormonal and behavioural stress responsiveness.
abstract: Ultradian release of glucocorticoids is thought to be essential for homeostasis and health. Furthermore, deviation from this pulsatile release pattern is considered to compromise resilience to stress-related disease, even after hormone levels have normalised. In the present study, we investigate how constant exposure to different concentrations of corticosterone affects diurnal and ultradian pulsatility. The rate of recovery in pulsatile hypothalamic-pituitary-adrenal (HPA) activity after withdrawal of exogenous corticosterone is also examined. Finally, the behavioural and neuroendocrine responsiveness to an audiogenic stressor is studied. Adrenally intact male rats were subcutaneously implanted with vehicle, 40% or 100% corticosterone pellets for 7 days. The continuous release of corticosterone from these implants abolished diurnal and ultradian corticosterone variation, as measured with high-frequency automated blood sampling. Pellet removal on post-surgery day 8 allowed rapid recovery of endogenous rhythms in animals previously exposed to daily average concentrations (40%) but not after exposure to high concentrations (100%) of corticosterone. Behavioural and neuroendocrine responsiveness to stress was distinctly different between the treatment groups. Audiogenic stimulation 1 day after pellet removal resulted in a similar corticosterone response in animals previously exposed to 40% corticosterone or vehicle. The 40% pellet group, however, showed less and shorter behavioural activity (i.e. locomotion, risk assessment) to noise stress compared to 100% corticosterone and vehicle-treated animals. In conclusion, unlike the animals impanted with 100% corticosterone, we find that basal HPA axis activity in the 40% group, which had mean daily levels of circulating corticosterone in the physiological range, rapidly reverts to the characteristic pulsatile pattern of corticosterone secretion. Upon reinstatement of the ultradian rhythm, and despite the fact that these animals did not differ from controls in their response to noise stress, they did show substantial changes in their behavioural response to stress.
authors.affiliation: Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research (LACDR)/Leiden University Medical Centre (LUMC), University of Leiden, Leiden, The Netherlands. r.a.sarabdjitsingh@lacdr.leidenuniv.nl
authors.forename: R A
authors.initials: RA
authors.lastname: Sarabdjitsingh
authors.forename: F
authors.initials: F
authors.lastname: Spiga
authors.forename: M S
authors.initials: MS
authors.lastname: Oitzl
authors.forename: Y
authors.initials: Y
authors.lastname: Kershaw
authors.forename: O C
authors.initials: OC
authors.lastname: Meijer
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
authors.forename: E R
authors.initials: ER
authors.lastname: de Kloet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013315:Stress, Psychological
chemical_list: D000893:Anti-Inflammatory Agents; D003345:Corticosterone
references.citation: Eur J Pharmacol. 2008 Apr 7;583(2-3):255-62
references.pmid: 18339373
references.citation: Front Biosci. 2006 Sep 01;11:2746-58
references.pmid: 16720347
references.citation: Neuropsychopharmacology. 2000 Nov;23(5):477-501
references.pmid: 11027914
references.citation: Neuroendocrinology. 1989 Aug;50(2):117-23
references.pmid: 2550833
references.citation: Endocrinology. 2008 Jul;149(7):3241-3
references.pmid: 18586914
references.citation: Am J Physiol. 1985 Nov;249(5 Pt 2):R527-32
references.pmid: 2998210
references.citation: Front Neuroendocrinol. 2007 Aug-Sep;28(2-3):72-96
references.pmid: 17544065
references.citation: J Clin Endocrinol Metab. 2010 Jun;95(6):2699-714
references.pmid: 20371667
references.citation: Endocrinology. 1988 Apr;122(4):1337-42
references.pmid: 2831027
references.citation: J Neuroendocrinol. 2006 Jul;18(7):526-33
references.pmid: 16774501
references.citation: Clin Chim Acta. 2005 Sep;359(1-2):189-94
references.pmid: 15904907
references.citation: Nat Cell Biol. 2009 Sep;11(9):1093-102
references.pmid: 19684579
references.citation: Endocr Rev. 2000 Feb;21(1):55-89
references.pmid: 10696570
references.citation: Cell Tissue Res. 2002 Jul;309(1):109-18
references.pmid: 12111541
references.citation: Ann N Y Acad Sci. 2004 Jun;1018:141-50
references.pmid: 15240363
references.citation: Novartis Found Symp. 2000;227:244-57; discussion 257-60
references.pmid: 10752074
references.citation: Endocrinology. 1988 Apr;122(4):1343-8
references.pmid: 2831028
references.citation: Eur J Neurosci. 1996 Apr;8(4):794-800
references.pmid: 9081630
references.citation: Neuropsychopharmacology. 2003 Jan;28(1):119-25
references.pmid: 12496947
references.citation: J Neurosci. 2003 Jun 15;23(12):4850-7
references.pmid: 12832507
references.citation: Endocr Rev. 1998 Jun;19(3):269-301
references.pmid: 9626555
references.citation: Trends Neurosci. 2008 Jan;31(1):1-7
references.pmid: 18063498
references.citation: Neuroscience. 1997 Sep;80(2):419-26
references.pmid: 9284345
references.citation: Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E1011-22
references.pmid: 18349112
references.citation: J Neuroendocrinol. 2001 Oct;13(10):905-11
references.pmid: 11679059
references.citation: Neurobiol Learn Mem. 2008 Oct;90(3):495-503
references.pmid: 18707011
references.citation: Neurobiol Aging. 1997 May-Jun;18(3):285-9
references.pmid: 9263193
references.citation: Proc Biol Sci. 2010 Jun 7;277(1688):1627-33
references.pmid: 20129987
references.citation: J Neurosci. 1995 Jan;15(1 Pt 1):61-9
references.pmid: 7823152
references.citation: Endocrinology. 2007 Nov;148(11):5470-7
references.pmid: 17690167
references.citation: Nat Rev Neurosci. 2005 Jun;6(6):463-75
references.pmid: 15891777
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13456-61
references.pmid: 10557342
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19204-7
references.pmid: 16361444
references.citation: Endocrinology. 2010 Mar;151(3):1177-86
references.pmid: 20080870
references.citation: J Cogn Neurosci. 2010 Jul;22(7):1362-72
references.pmid: 19445601
references.citation: Endocrinology. 1998 Oct;139(10):4044-52
references.pmid: 9751481
references.citation: Endocrinology. 1998 Feb;139(2):443-50
references.pmid: 9449609
references.citation: Neuroendocrinology. 1988 Oct;48(4):439-44
references.pmid: 3211285
references.citation: J Neuroendocrinol. 2007 Nov;19(11):891-900
references.pmid: 17927667
references.citation: J Endocrinol. 2009 Jan;200(1):3-22
references.pmid: 18971218
references.citation: Psychoneuroendocrinology. 2004 Jun;29(5):618-35
references.pmid: 15041085
references.citation: Endocrinology. 1992 Aug;131(2):585-94
references.pmid: 1322275
references.citation: Endocrinology. 1996 Nov;137(11):4935-43
references.pmid: 8895366
references.citation: J Neuroendocrinol. 1997 Aug;9(8):577-88
references.pmid: 9283046
references.citation: J Endocrinol. 2008 Feb;196(2):323-30
references.pmid: 18252955
references.citation: Front Neuroendocrinol. 2004 Jul;25(2):69-76
references.pmid: 15571755
references.citation: J Clin Endocrinol Metab. 1997 Jan;82(1):234-8
references.pmid: 8989265
references.citation: Am J Physiol. 1982 Oct;243(4):E310-8
references.pmid: 6889816
references.citation: J Neuroendocrinol. 2004 Jun;16(6):550-7
references.pmid: 15189330
references.citation: Brain Res. 1994 Jun 27;649(1-2):27-35
references.pmid: 7953642
references.citation: Am J Physiol. 1991 Nov;261(5 Pt 2):R1257-68
references.pmid: 1951775
references.citation: J Neuroendocrinol. 2003 Jun;15(6):607-13
references.pmid: 12716412