Recovery from disrupted ultradian glucocorticoid rhythmicity reveals a dissociation between hormonal and behavioural stress responsiveness.
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.
Sarabdjitsingh
R A
RA
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
Spiga
F
F
Oitzl
M S
MS
Kershaw
Y
Y
Meijer
O C
OC
Lightman
S L
SL
de Kloet
E R
ER
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
D000893:Anti-Inflammatory Agents; D003345:Corticosterone
Eur J Pharmacol. 2008 Apr 7;583(2-3):255-62
18339373
Front Biosci. 2006 Sep 01;11:2746-58
16720347
Neuropsychopharmacology. 2000 Nov;23(5):477-501
11027914
Neuroendocrinology. 1989 Aug;50(2):117-23
2550833
Endocrinology. 2008 Jul;149(7):3241-3
18586914
Am J Physiol. 1985 Nov;249(5 Pt 2):R527-32
2998210
Front Neuroendocrinol. 2007 Aug-Sep;28(2-3):72-96
17544065
J Clin Endocrinol Metab. 2010 Jun;95(6):2699-714
20371667
Endocrinology. 1988 Apr;122(4):1337-42
2831027
J Neuroendocrinol. 2006 Jul;18(7):526-33
16774501
Clin Chim Acta. 2005 Sep;359(1-2):189-94
15904907
Nat Cell Biol. 2009 Sep;11(9):1093-102
19684579
Endocr Rev. 2000 Feb;21(1):55-89
10696570
Cell Tissue Res. 2002 Jul;309(1):109-18
12111541
Ann N Y Acad Sci. 2004 Jun;1018:141-50
15240363
Novartis Found Symp. 2000;227:244-57; discussion 257-60
10752074
Endocrinology. 1988 Apr;122(4):1343-8
2831028
Eur J Neurosci. 1996 Apr;8(4):794-800
9081630
Neuropsychopharmacology. 2003 Jan;28(1):119-25
12496947
J Neurosci. 2003 Jun 15;23(12):4850-7
12832507
Endocr Rev. 1998 Jun;19(3):269-301
9626555
Trends Neurosci. 2008 Jan;31(1):1-7
18063498
Neuroscience. 1997 Sep;80(2):419-26
9284345
Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E1011-22
18349112
J Neuroendocrinol. 2001 Oct;13(10):905-11
11679059
Neurobiol Learn Mem. 2008 Oct;90(3):495-503
18707011
Neurobiol Aging. 1997 May-Jun;18(3):285-9
9263193
Proc Biol Sci. 2010 Jun 7;277(1688):1627-33
20129987
J Neurosci. 1995 Jan;15(1 Pt 1):61-9
7823152
Endocrinology. 2007 Nov;148(11):5470-7
17690167
Nat Rev Neurosci. 2005 Jun;6(6):463-75
15891777
Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13456-61
10557342
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19204-7
16361444
Endocrinology. 2010 Mar;151(3):1177-86
20080870
J Cogn Neurosci. 2010 Jul;22(7):1362-72
19445601
Endocrinology. 1998 Oct;139(10):4044-52
9751481
Endocrinology. 1998 Feb;139(2):443-50
9449609
Neuroendocrinology. 1988 Oct;48(4):439-44
3211285
J Neuroendocrinol. 2007 Nov;19(11):891-900
17927667
J Endocrinol. 2009 Jan;200(1):3-22
18971218
Psychoneuroendocrinology. 2004 Jun;29(5):618-35
15041085
Endocrinology. 1992 Aug;131(2):585-94
1322275
Endocrinology. 1996 Nov;137(11):4935-43
8895366
J Neuroendocrinol. 1997 Aug;9(8):577-88
9283046
J Endocrinol. 2008 Feb;196(2):323-30
18252955
Front Neuroendocrinol. 2004 Jul;25(2):69-76
15571755
J Clin Endocrinol Metab. 1997 Jan;82(1):234-8
8989265
Am J Physiol. 1982 Oct;243(4):E310-8
6889816
J Neuroendocrinol. 2004 Jun;16(6):550-7
15189330
Brain Res. 1994 Jun 27;649(1-2):27-35
7953642
Am J Physiol. 1991 Nov;261(5 Pt 2):R1257-68
1951775
J Neuroendocrinol. 2003 Jun;15(6):607-13
12716412