title: Sleep allostasis in chronic sleep restriction: the role of the norepinephrine system.
abstract: Sleep responses to chronic sleep restriction may be very different from those observed after acute total sleep deprivation. Specifically, when sleep restriction is repeated for several consecutive days, animals express attenuated compensatory increases in sleep time and intensity during daily sleep opportunities. The neurobiological mechanisms underlying these adaptive, or more specifically, allostatic, changes in sleep homeostasis are unknown. Several lines of evidence indicate that norepinephrine may play a key role in modulating arousal states and NREM EEG delta power, which is widely recognized as a marker for sleep intensity. Therefore, we investigated time course changes in brain adrenergic receptor mRNA levels in response to chronic sleep restriction using a rat model. Here, we observed that significantly altered mRNA levels of the α1- adrenergic receptor in the basal forebrain as well as α2- and β1-adrenergic receptor in the anterior cingulate cortex only on the first sleep restriction day. On the other hand, the frontal cortex α1-, α2-, and β1-adrenergic receptor mRNA levels were reduced throughout the period of sleep restriction. Combined with our earlier findings on EEG that sleep time and intensity significantly increased only on the first sleep restriction days, these results suggest that alterations in the brain norepinephrine system in the basal forebrain and cingulate cortex may mediate allostatic changes in sleep time and intensity observed during chronic sleep restriction.
authors.affiliation: VA Boston Healthcare System, Research Service and Harvard Medical School, Department of Psychiatry, 940 Belmont St., Brockton, MA 02301-5596, USA. youngsoo_kim@hms.harvard.edu
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Lichao
authors.initials: L
authors.lastname: Chen
authors.forename: Robert W
authors.initials: RW
authors.lastname: McCarley
authors.forename: Robert E
authors.initials: RE
authors.lastname: Strecker
mesh_terms: D052636:Allostasis / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D004569:Electroencephalography / Q000379:methods; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D009638:Norepinephrine
keywords: AR; Allostasis; BL; CSR; Chronic sleep restriction; HSD; LC; NE; NREM; Norepinephrine; R; REM; Rat; SD; SO; SR; WKY; Wistar-Kyoto; ZT; adrenergic receptor; baseline; chronic sleep restriction; homeostatic sleep derive; locus coeruleus; non-rapid eye movement; norepinephrine; qRT-PCR; quantitative reverse transcription-polymerase chain reaction; rapid eye movement; recovery sleep; sleep deprivation; sleep opportunity; sleep restriction; zeitgeber time
references.citation: Brain Res. 1982 Mar 11;235(2):393-6
references.pmid: 6329418
references.citation: Am J Physiol Regul Integr Comp Physiol. 2012 Jun 15;302(12):R1411-25
references.pmid: 22492816
references.citation: Brain Res Bull. 1983 Dec;11(6):729-34
references.pmid: 6318919
references.citation: Brain Behav Immun. 2012 May;26(4):672-9
references.pmid: 22433899
references.citation: Brain Res Mol Brain Res. 1998 Jun 15;57(2):235-40
references.pmid: 9675421
references.citation: Brain Res. 2000 Mar 31;860(1-2):181-9
references.pmid: 10727641
references.citation: Sleep. 1999 Feb 1;22(1):11-31
references.pmid: 9989363
references.citation: J Neurosci. 1981 Jun;1(6):641-9
references.pmid: 7346572
references.citation: Neuroreport. 2013 Jan 23;24(2):91-5
references.pmid: 23238166
references.citation: J Neurosci. 1989 Nov;9(11):4062-7
references.pmid: 2511282
references.citation: Nat Neurosci. 2010 Dec;13(12):1526-33
references.pmid: 21037585
references.citation: J Neurosci. 2005 May 4;25(18):4503-11
references.pmid: 15872097
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15939-44
references.pmid: 20696898
references.citation: Physiol Behav. 1994 Jun;55(6):997-1003
references.pmid: 8047591
references.citation: Neurosci Biobehav Rev. 2008;32(1):99-117
references.pmid: 17764741
references.citation: Am J Physiol. 1998 Aug;275(2):R555-65
references.pmid: 9688693
references.citation: Psychoneuroendocrinology. 2009 Oct;34(9):1346-54
references.pmid: 19450933
references.citation: J Neurosci Res. 2005 Dec 1;82(5):650-8
references.pmid: 16273548
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11696-701
references.pmid: 12975524
references.citation: J Sleep Res. 2003 Mar;12(1):1-12
references.pmid: 12603781
references.citation: J Neurosci. 1981 Aug;1(8):876-86
references.pmid: 7346592
references.citation: Brain Res. 1993 Feb 5;602(2):221-7
references.pmid: 8448668
references.citation: Trends Pharmacol Sci. 2005 Nov;26(11):578-86
references.pmid: 16183137
references.citation: Horm Behav. 2003 Jan;43(1):2-15
references.pmid: 12614627
references.citation: Ann N Y Acad Sci. 2008 Oct;1141:105-30
references.pmid: 18991954
references.citation: J Neurosci. 2010 Oct 27;30(43):14543-51
references.pmid: 20980612
references.citation: Sleep. 1994 Oct;17(7):583-9
references.pmid: 7531362
references.citation: Sleep. 2003 Mar 15;26(2):117-26
references.pmid: 12683469
references.citation: Brain Res Rev. 2008 Jun;58(1):1-17
references.pmid: 18199483
references.citation: Sleep Med Rev. 2012 Apr;16(2):187-97
references.pmid: 22296742
references.citation: Eur J Neurosci. 2004 May;19(10):2741-52
references.pmid: 15147308
references.citation: Neuroscience. 2010 Sep 1;169(3):1115-26
references.pmid: 20542093
references.citation: Neuroreport. 2001 Jun 13;12(8):1577-80
references.pmid: 11409719
references.citation: Eur J Neurosci. 1989 May;1(3):181-188
references.pmid: 12106149
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Dec;29(8):1214-24
references.pmid: 16226365
references.citation: Neurochem Res. 2006 Aug;31(8):1095-102
references.pmid: 16933152
references.citation: Metabolism. 2006 Oct;55(10 Suppl 2):S20-3
references.pmid: 16979422
references.citation: Prog Neurobiol. 2004 Aug;73(6):379-96
references.pmid: 15313333
references.citation: Sleep Med Rev. 2009 Jun;13(3):187-94
references.pmid: 18848476
references.citation: Pharmacol Biochem Behav. 1981 Jul;15(1):149-51
references.pmid: 7197363
references.citation: J Investig Dermatol Symp Proc. 1997 Aug;2(1):69-75
references.pmid: 9487019
references.citation: Physiol Behav. 1989 Feb;45(2):289-97
references.pmid: 2756014
references.citation: Psychophysiology. 1981 Mar;18(2):107-13
references.pmid: 6111825
references.citation: Physiol Behav. 1989 Dec;46(6):993-8
references.pmid: 2634265
references.citation: Nature. 1985 Sep 12-18;317(6033):124-9
references.pmid: 2993919
references.citation: Neuroreport. 2007 Dec 3;18(18):1895-9
references.pmid: 18007182
references.citation: Sleep. 2012 Jun 01;35(6):861-9
references.pmid: 22654205
references.citation: Sleep. 2010 Sep;33(9):1147-57
references.pmid: 20857860
references.citation: Eur J Neurosci. 2006 Oct;24(7):2039-48
references.pmid: 17067300
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Am J Physiol. 1994 Feb;266(2 Pt 2):R353-60
references.pmid: 8141389
references.citation: N Engl J Med. 1998 Jan 15;338(3):171-9
references.pmid: 9428819
references.citation: Eur J Neurosci. 2003 Aug;18(3):723-7
references.pmid: 12911769
references.citation: J Physiol Paris. 1993;87(4):229-38
references.pmid: 8136789
references.citation: Am J Physiol. 1995 Jun;268(6 Pt 2):R1456-63
references.pmid: 7611522
references.citation: J Sleep Res. 2006 Dec;15(4):386-94
references.pmid: 17118095
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10697-702
references.pmid: 17548824