Altered neural cholinergic receptor systems in cocaine-addicted subjects.
Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.
Adinoff
Bryon
B
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8564, USA. bryon.adinoff@utsouthwestern.edu
Devous
Michael D
MD
Williams
Mark J
MJ
Best
Susan E
SE
Harris
Thomas S
TS
Minhajuddin
Abu
A
Zielinski
Tanya
T
Cullum
Munro
M
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging* / Q000187:drug effects; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage; D011569:Psychiatric Status Rating Scales; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012601:Scopolamine / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D010830:Physostigmine; D012601:Scopolamine
Neurosci Biobehav Rev. 2004 Jan;27(8):841-50
15019433
Science. 2007 Jan 26;315(5811):531-4
17255515
J Neurosci. 2004 Nov 10;24(45):10117-27
15537882
J Nucl Med. 2007 Oct;48(10):1633-40
17873128
Biol Psychiatry. 2002 Apr 15;51(8):605-11
11955460
Neurosci Lett. 1999 Dec 24;277(2):115-8
10624823
Arch Gen Psychiatry. 2008 Mar;65(3):310-8
18316677
Neuroscience. 1999;89(4):1209-17
10362308
Eur J Pharmacol. 2003 Nov 7;480(1-3):117-23
14623355
Brain Res. 1993 Aug 6;618(2):341-5
8104086
Neuroscience. 2003;120(4):1149-56
12927219
Am J Psychiatry. 1998 Jan;155(1):124-6
9433350
Brain Res. 1985 Dec 2;348(2):355-8
4075093
Psychopharmacology (Berl). 2002 Oct;163(3-4):362-80
12373437
Mol Pharmacol. 1992 Apr;41(4):736-42
1569924
Neuroscientist. 2003 Feb;9(1):23-36
12580337
Neuroimage. 2003 Jul;19(3):1095-102
12880835
Cell Mol Neurobiol. 2004 Feb;24(1):129-36
15049517
Neuroscience. 2000;101(2):277-82
11074150
J Cereb Blood Flow Metab. 1998 Oct;18(10):1130-42
9778190
J Neurosci. 2006 May 31;26(22):6004-10
16738243
Neuropsychopharmacology. 2008 Jul;33(8):1779-97
17928814
Neuropsychopharmacology. 2002 Mar;26(3):376-86
11850152
Am J Addict. 2005 Mar-Apr;14(2):106-23
16019961
Brain Res. 1991 Jun 21;552(1):27-35
1655167
Behav Neurosci. 2006 Apr;120(2):401-12
16719704
Brain Res. 1988 Aug 9;457(2):383-5
3219565
J Clin Exp Neuropsychol. 2005 Feb;27(2):189-204
15903150
Arch Gen Psychiatry. 2001 Apr;58(4):334-41
11296093
Neuroimage. 1997 Nov;6(4):335-43
9417975
J Addict Dis. 2007;26 Suppl 1:25-39
19283972
Eur J Nucl Med. 1999 Feb;26(2):135-43
9933347
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3233-43
18640922
Curr Opin Neurobiol. 2003 Aug;13(4):500-5
12965300
Psychopharmacology (Berl). 1987;93(1):31-5
3114812
Behav Brain Res. 1995 Feb;67(1):1-27
7748496
Biochemistry. 1986 Apr 8;25(7):1777-85
2423116
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7050-4
2402490
Psychopharmacology (Berl). 1999 Mar;143(1):47-53
10227079
Neuroreport. 2004 Oct 5;15(14):2173-6
15371727
J Neurosci. 2002 Aug 1;22(15):6347-52
12151512
Addiction. 2005 Mar;100 Suppl 1:68-77
15730351
Brain Res. 1995 Apr 10;676(2):378-85
7614009
Neurobiol Learn Mem. 2003 Nov;80(3):245-56
14521867
Eur J Pharmacol. 1993 Jul 20;238(2-3):377-81
8405105
Lancet. 1990 Jun 23;335(8704):1484-7
1972432
Pharmacol Biochem Behav. 1982 Dec;17(6):1295-9
7163358
Learn Mem. 2004 Jan-Feb;11(1):70-7
14747519
Learn Mem. 2004 Sep-Oct;11(5):641-7
15466320
Synapse. 2000 Dec 1;38(3):313-21
11020234
Am J Psychiatry. 2003 Feb;160(2):323-33
12562580
Life Sci. 2001 Apr 27;68(22-23):2449-56
11392612
J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52
3047364
Am J Psychiatry. 1997 Jul;154(7):918-25
9210741
Ann N Y Acad Sci. 2004 Oct;1025:351-62
15542736
Biol Psychiatry. 2002 Jan 15;51(2):134-42
11822992
Arch Gen Psychiatry. 2006 Aug;63(8):907-15
16894067
Mol Imaging Biol. 2007 Jul-Aug;9(4):243-57
17318670
J Neurosci. 2005 Sep 7;25(36):8141-9
16148222
Neuropsychopharmacology. 2006 Mar;31(3):644-50
16123763
Int J Neuropsychopharmacol. 2008 Sep;11(6):729-41
18248689
Biol Psychiatry. 2005 Mar 1;57(5):487-94
15737663
Psychol Med. 1983 Aug;13(3):595-605
6622612
Biol Psychiatry. 2002 Jun 1;51(11):890-5
12022962
Neuroscience. 2003;117(2):477-83
12614687
J Clin Endocrinol Metab. 2001 Feb;86(2):679-84
11158031
J Neurosci Res. 2003 Oct 1;74(1):91-6
13130510
Am J Psychiatry. 2000 Nov;157(11):1789-98
11058476
Brain Res. 1994 Jan 28;635(1-2):196-202
8173955
Chem Biol Interact. 2008 Sep 25;175(1-3):227-30
18501884
Pharmacol Biochem Behav. 1973 Nov-Dec;1(6):643-9
4206608
Neuroscience. 1996 Feb;70(3):653-60
9045078
J Neurosci. 2008 Mar 5;28(10):2516-26
18322096
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12040-5
8876259
Arch Gen Psychiatry. 2005 Jul;62(7):761-8
15997017
J Neurochem. 2004 Jan;88(2):502-12
14690538
Am J Psychiatry. 2005 Mar;162(3):567-77
15741475
Prog Brain Res. 1996;109:285-97
9009717
Eur J Neurosci. 2004 Aug;20(4):1081-8
15305877
Neurology. 1999 Mar 10;52(4):691-9
10078712
J Clin Exp Neuropsychol. 1995 Aug;17(4):611-21
7593479
Arch Gen Psychiatry. 1990 Sep;47(9):861-8
2393345
Gend Med. 2006 Sep;3(3):206-22
17081954
Pharmacol Biochem Behav. 2000 Jul;66(3):475-81
10899358
Pharmacol Biochem Behav. 1999 Jan;62(1):15-20
9972840
Synapse. 2007 Jan;61(1):29-36
17068780
J Comp Neurol. 2005 Nov 7;492(1):34-49
16175554
Neuroimage. 2005 Jul 15;26(4):1097-108
15886020