Role of adenosine and wake-promoting basal forebrain in insomnia and associated sleep disruptions caused by ethanol dependence.
Insomnia is a severe symptom of alcohol withdrawal; however, the underlying neuronal mechanism is yet unknown. We hypothesized that chronic ethanol exposure will impair basal forebrain (BF) adenosinergic mechanism resulting in insomnia-like symptoms. We performed a series of experiments in Sprague-Dawley rats to test our hypothesis. We used Majchrowicz's chronic binge ethanol protocol to induce ethanol dependency. Our first experiment verified the effects of ethanol withdrawal on sleep-wakefulness. Significant increase in wakefulness was observed during ethanol withdrawal. Next, we examined c-Fos expression (marker of neuronal activation) in BF wake-promoting neurons during ethanol withdrawal. There was a significant increase in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Our third experiment examined the effects of ethanol withdrawal on sleep deprivation induced increase in BF adenosine levels. Sleep deprivation did not increase BF adenosine levels in ethanol dependent rats. Our last experiment examined the effects of ethanol withdrawal on equilibrative nucleoside transporter 1 and A1 receptor expression in the BF. There was a significant reduction in A1 receptor and equilibrative nucleoside transporter 1 expression in the BF of ethanol dependent rats. Based on these results, we suggest that insomnia observed during ethanol withdrawal is caused because of impaired adenosinergic mechanism in the BF.
Sharma
Rishi
R
Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, Missouri 65210, USA.
Engemann
Samuel
S
Sahota
Pradeep
P
Thakkar
Mahesh M
MM
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000437:Alcoholism / Q000150:complications* / Q000503:physiopathology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002452:Cell Count; D033721:Equilibrative Nucleoside Transporter 1; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D016548:Prosencephalon / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology* / Q000503:physiopathology*; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D014851:Wakefulness / Q000502:physiology*
D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; C438652:Slc29a1 protein, rat; D012313:RNA; D000241:Adenosine
J Stud Alcohol. 1978 Jul;39(7):1213-23
212646
Neuroscience. 2007 Jul 13;147(3):811-23
17574765
Am J Physiol. 1999 Nov;277(5):R1488-92
10564223
Sleep. 2009 Oct;32(10):1341-52
19848363
J Comp Neurol. 2006 Oct 10;498(5):667-89
16917819
Brain Res Bull. 2006 Dec 11;71(1-3):287-95
17113958
Eur J Neurosci. 2006 Oct;24(7):2039-48
17067300
J Neurosci. 2008 Jan 9;28(2):491-504
18184792
Physiol Rev. 2008 Jul;88(3):1183-241
18626069
J Neurosci. 2006 Aug 2;26(31):8092-100
16885223
Clin Ther. 1994 Sep-Oct;16(5):873-97; discussion 854
7859246
Alcohol Res Health. 2001;25(2):101-9
11584549
Brain Res Mol Brain Res. 2001 Apr 18;89(1-2):153-7
11311986
Exp Neurol. 2000 May;163(1):264-70
10785466
Neuroscience. 2008 Jun 2;153(4):875-80
18440150
Curr Protoc Neurosci. 2008 Jul;Chapter 9:Unit 9.28
18634000
Alcohol. 1999 Oct;19(2):157-62
10548160
Eur J Pharmacol. 1988 Aug 9;153(1):141-5
2850926
Arch Ital Biol. 2001 Apr;139(3):313-28
11330208
Sleep Med. 2007 Jun;8(4):302-30
17468046
Alcohol. 2010 Feb;44(1):89-98
20113877
Brain Res Bull. 2009 Dec 16;80(6):382-8
19716862
J Pharmacol Exp Ther. 1984 Feb;228(2):268-74
6694111
Alcohol Clin Exp Res. 1998 Nov;22(8):1796-802
9835298
Psychopharmacologia. 1973;33(2):135-40
4359814
EXS. 1989;57:159-71
2533089
Behav Brain Res. 2000 Nov;115(2):117-41
11000416
Science. 1997 May 23;276(5316):1265-8
9157887
J Sleep Res. 2003 Dec;12(4):299-304
14633241
Biochem Cell Biol. 1998;76(5):761-70
10353709
Pharmacol Biochem Behav. 1996 Feb;53(2):249-55
8808128
Acta Physiol (Oxf). 2010 Mar;198(3):223-35
19723027
J Nerv Ment Dis. 1971 Dec;153(6):424-33
4330827
Alcohol Clin Exp Res. 1998 Nov;22(8):1864-71
9835309
Med Hypotheses. 2010 May;74(5):928-33
19910125
Eur J Neurosci. 2000 Jun;12(6):2166-84
10886356
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
Alcohol Clin Exp Res. 2002 Aug;26(8):1153-61
12198389
Neuroscience. 2008 Nov 11;157(1):238-53
18805464
Sleep. 1995 Jul;18(6):478-500
7481420
Nat Protoc. 2008;3(6):1101-8
18546601
Brain Res Bull. 2001 Jul 1;55(4):513-20
11543952
Neuroreport. 2000 Feb 28;11(3):437-40
10718290
Brain Res. 1997 Feb 28;749(2):263-74
9138726
Alcohol Alcohol. 2009 Mar-Apr;44(2):115-27
18940959
Prog Neurobiol. 2004 Aug;73(6):379-96
15313333
Brain Res. 2007 Oct 12;1174:47-52
17854781
Alcohol Clin Exp Res. 1999 Jan;23(1):134-40
10029214
Neuroscience. 2006 Jun 30;140(2):403-13
16542780
J Neurosci. 2009 Sep 23;29(38):11828-40
19776269
Ann N Y Acad Sci. 2008;1129:275-86
18591488
Alcohol Clin Exp Res. 2006 Jul;30(7):1214-22
16792570
Alcohol. 2000 Feb;20(2):173-9
10719796
Psychopharmacology (Berl). 2005 Oct;181(4):714-21
15983797
Brain Res. 2008 May 7;1208:120-7
18387599
Neuropsychopharmacology. 2006 Oct;31(10):2210-20
16407902
Eur J Pharmacol. 1997 Apr 4;323(2-3):R5-7
9128854
Alcohol Res Health. 2001;25(2):110-25
11584550
J Neurosci. 2003 May 15;23(10):4278-87
12764116
J Neurosci Methods. 1989 Sep;29(3):261-5
2507830
Neuroreport. 2007 Dec 3;18(18):1895-9
18007182
Biol Psychiatry. 1990 Mar 1;27(5):477-88
2310803
Neuroscience. 2003;122(4):1107-13
14643776
Annu Rev Neurosci. 2001;24:31-55
11283304
Alcohol Alcohol Suppl. 1993;2:425-9
7748333
Neuroscience. 2004;123(2):361-70
14698744
J Biol Chem. 1990 Feb 5;265(4):1946-51
2298733
Alcohol Clin Exp Res. 2010 Jun;34(6):997-1005
20374215
J Physiol. 1999 Dec 15;521 Pt 3:679-90
10601498
J Neuroendocrinol. 2008 Jun;20(6):665-72
18601687
J Pharmacol Exp Ther. 1970 Oct;175(1):94-112
4319478
Pharmacol Biochem Behav. 1998 Apr;59(4):955-60
9586855
Arch Gen Psychiatry. 1994 Mar;51(3):189-97
8122956
Alcohol Health Res World. 1998;22(1):73-9
15706737
Alcohol Clin Exp Res. 2004 Feb;28(2):350-64
15112943
Behav Brain Res. 2009 Mar 2;198(1):113-24
19014977
Mol Vis. 2008 May 30;14:1020-7
18523665
Alcohol Clin Exp Res. 2010 May;34(5):813-8
20184564
Neurosci Biobehav Rev. 2007;31(5):775-824
17445891
Prog Brain Res. 2004;145:157-69
14650914
Psychopharmacologia. 1975 Sep 17;43(3):245-54
1237914
Neuroreport. 2009 Jul 15;20(11):1013-8
19491711
Alcohol Clin Exp Res. 1981 Spring;5(2):318-25
7018314