Cognitive effects of nicotine: genetic moderators.
Cigarette smoking is the main preventable cause of death in developed countries, and the development of more effective treatments is necessary. Cumulating evidence suggests that cognitive enhancement may contribute to the addictive actions of nicotine. Several studies have demonstrated that nicotine enhances cognitive performance in both smokers and non-smokers. Genetic studies support the role of both dopamine (DA) and nicotinic acetylcholine receptors (nAChRs) associated with nicotine-induced cognitive enhancement. Based on knockout mice studies, beta2 nAChRs are thought to be essential in mediating the cognitive effects of nicotine. alpha7nAChRs are associated with attentional and sensory filtering response, especially in schizophrenic individuals. Genetic variation in D2 type DA receptors and the catechol-O-methyltransferase enzyme appears to moderate cognitive deficits induced by smoking abstinence. Serotonin transporter (5-HTT) gene variation also moderates nicotine-induced improvement in spatial working memory. Less is known about the contribution of genetic variation in DA transporter and D4 type DA receptor genetic variation on the cognitive effects of nicotine. Future research will provide a clearer understanding of the mechanism underlying the cognitive-enhancing actions of nicotine.
Herman
Aryeh I
AI
Department of Psychiatry and VA Connecticut Healthcare System, School of Medicine, Yale University, West Haven, CT 06516, USA.
Sofuoglu
Mehmet
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000503:physiopathology
D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; D050486:Serotonin Plasma Membrane Transport Proteins; D009538:Nicotine; D002394:Catechol O-Methyltransferase
Neuroscience. 1995 Jan;64(2):385-95
7700528
Addiction. 2003 Jan;98(1):23-31
12492752
Am J Med Genet. 2000 Jun 12;96(3):331-4
10898910
Brain Res. 2000 Jul 14;871(1):66-74
10882784
Psychopharmacology (Berl). 2007 May;191(4):919-29
17225162
Ann N Y Acad Sci. 2008;1129:200-12
18591481
Trends Neurosci. 2005 Jul;28(7):371-8
15979501
Neuropsychopharmacology. 2000 Oct;23(4):351-64
10989262
Nicotine Tob Res. 2004 Apr;6(2):229-39
15203796
Addiction. 1998 Mar;93(3):317-20
10328040
Psychol Addict Behav. 2000 Jun;14(2):111-20
10860110
Neuropsychopharmacology. 2008 Mar;33(4):715-20
17534380
Trends Neurosci. 2000 Oct;23(10 Suppl):S34-40
11052218
Behav Pharmacol. 2008 Sep;19(5-6):630-40
18690117
Handb Exp Pharmacol. 2009;(192):209-33
19184651
Science. 1996 Nov 29;274(5292):1527-31
8929413
Nicotine Tob Res. 1999;1 Suppl 2:S143-7; discussion S165-6
11768172
Neuroreport. 1999 Jun 3;10(8):1779-82
10501574
Exp Clin Psychopharmacol. 2009 Apr;17(2):91-8
19331485
Am J Med Sci. 2003 Oct;326(4):168-73
14557728
Genes Brain Behav. 2006 Aug;5(6):433-40
16923147
J Cell Mol Med. 2008 Sep-Oct;12(5A):1672-6
18194457
J Hum Genet. 2004;49(1):35-39
14685824
Mol Psychiatry. 2001 Jul;6(4):425-8
11443527
Psychopharmacology (Berl). 1998 Apr;136(4):320-7
9600576
J Pediatr. 2008 Feb;152(2):263-9
18206700
Pharmacogenomics J. 2003;3(4):242-7
12931138
J Neurobiol. 2002 Dec;53(4):457-78
12436413
Am J Psychiatry. 2004 Jul;161(7):1224-30
15229055
Pharmacol Biochem Behav. 2001 Dec;70(4):561-70
11796154
Psychopharmacology (Berl). 2007 Mar;190(4):449-56
17206495
J Neurosci. 2008 Apr 2;28(14):3769-80
18385335
J Chem Neuroanat. 1997 Jul;13(2):105-13
9285355
Psychopharmacology (Berl). 2007 Mar;190(4):457-67
17205318
Nicotine Tob Res. 1999;1 Suppl 2:S51-7; discussion S69-70
11768187
Addict Biol. 2009 Jan;14(1):32-42
18855804
Drug Alcohol Depend. 1993 Dec;34(1):11-8
8174498
Addict Behav. 1998 Mar-Apr;23(2):263-6
9573430
Pharmacogenet Genomics. 2008 Feb;18(2):121-8
18192898
J Neurochem. 2001 Dec;79(5):1033-8
11739616
J Neural Transm (Vienna). 1997;104(10):1005-14
9503253
Neuroimage. 2003 Jul;19(3):1002-13
12880828
Science. 2006 Oct 20;314(5798):475-8
17053149
Nicotine Tob Res. 2003 Apr;5(2):245-54
12745498
Neurosci Lett. 2006 Jan 30;393(2-3):206-10
16246492
Mol Psychiatry. 2002;7(1):44-55
11803445
Psychopharmacology (Berl). 2008 Mar;197(1):95-105
18038223
Eur J Nucl Med Mol Imaging. 2003 Feb;30(2):306-11
12552351
Neurosci Lett. 2004 Jun 3;363(1):29-32
15157990
Neurosci Lett. 2002 Dec 13;334(2):135-9
12435490
Epilepsia. 1999;40 Suppl 3:9-11
10446744
Arch Gen Psychiatry. 1986 Mar;43(3):289-94
3954551
Pharmacol Biochem Behav. 2004 Jul;78(3):639-45
15251273
Br J Pharmacol. 2008 Feb;153(4):792-804
18059317
Neurology. 1998 Dec;51(6):1608-12
9855510
Psychopharmacology (Berl). 2009 Nov;207(1):153-62
19693492
J Neurosci. 2003 Apr 15;23(8):3176-85
12716925
Neuropsychopharmacology. 2009 Feb;34(3):717-28
18704100
Behav Genet. 1999 Nov;29(6):383-93
10857244
Brain Res Bull. 1998 Apr;45(6):577-82
9566501
Pharmacogenomics J. 2008 Apr;8(2):122-8
17387332
Neuropharmacology. 2003 Sep;45(3):334-44
12871651
Am J Epidemiol. 2002 Dec 1;156(11):994-1001
12446255
J Pharmacol Exp Ther. 1989 Dec;251(3):976-82
2600826
Exp Clin Psychopharmacol. 2009 Jun;17(3):173-80
19586232
J Neurochem. 1995 Sep;65(3):1157-65
7643093
Psychopharmacology (Berl). 2006 Mar;184(3-4):523-39
16220335
Psychopharmacology (Berl). 1992;107(2-3):285-9
1615127
J Consult Clin Psychol. 1993 Oct;61(5):743-50
8245272
Mol Pharmacol. 1997 Mar;51(3):499-506
9058606
Eur J Neurosci. 2004 Jul;20(1):120-6
15245485
Biochem Pharmacol. 2007 Oct 15;74(8):1102-11
17597586
Schizophr Bull. 2006 Oct;32(4):692-700
16469942
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9596-601
12876201
Hum Mol Genet. 2007 Jan 1;16(1):36-49
17135278
Neuroscience. 1997 Dec;81(4):1009-17
9330363
Brain Res. 2001 Feb 23;892(2):269-80
11172774
J Pharmacol Exp Ther. 1966 Nov;154(2):350-6
5950956
Neuroscience. 2006 Feb;137(3):853-64
16309846
Genes Brain Behav. 2008 Mar;7(2):164-72
17559419
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):587-92
9012828
Acta Paediatr. 2006 Jun;95(6):645-9
16754543
Eur J Neurosci. 2000 May;12(5):1827-37
10792459
Annu Rev Pharmacol Toxicol. 2009;49:57-71
18834313
Biochem Pharmacol. 2009 Oct 1;78(7):658-67
19406107
Prog Neurobiol. 2002 May;67(1):53-83
12126656
Biol Psychiatry. 2009 Apr 15;65(8):671-9
19058786
Behav Genet. 2006 Sep;36(5):627-39
16823639
J Neurochem. 2003 Mar;84(6):1431-41
12614343
Nature. 1996 Feb 15;379(6566):606-12
8628395
Neuron. 2002 Oct 10;36(2):213-28
12383778
Mol Neurobiol. 2008 Aug;38(1):101-21
18690555
MMWR Morb Mortal Wkly Rep. 2005 Nov 11;54(44):1121-4
16280969
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):529-37
11999904
Neuropsychopharmacology. 2003 Jul;28(7):1366-73
12784106
Eur Psychiatry. 2008 Sep;23(6):385-9
18755576
J Pediatr. 2003 Jul;143(1):104-10
12915833
Prog Neurobiol. 2007 Oct;83(2):69-91
17681661
Nature. 2005 Jul 7;436(7047):103-7
16001069
Arch Gen Psychiatry. 2007 Sep;64(9):1078-86
17768273
Am J Psychiatry. 1998 Oct;155(10):1325-31
9766762
Pharmacol Toxicol. 1994 Dec;75(6):348-52
7534921
Neurosci Lett. 2009 Apr 10;453(3):131-4
19429020
Behav Brain Res. 2009 Jan 23;196(2):207-13
18831991
Neuropsychopharmacology. 2008 Dec;33(13):3069-77
18580877
Psychopharmacology (Berl). 2008 May;198(1):93-101
18338158
Neuropsychopharmacology. 2004 May;29(5):891-900
14970827
J Pharmacol Exp Ther. 1994 Jul;270(1):319-28
7913497
Biol Psychiatry. 1995 Jul 1;38(1):22-33
7548469
Biol Psychiatry. 2003 Dec 1;54(11):1222-33
14643090
J Med Chem. 2000 Nov 2;43(22):4045-50
11063601
Hum Mol Genet. 2005 May 1;14(9):1211-9
15790597
Am J Psychiatry. 1993 Dec;150(12):1856-61
8238642
Prog Drug Res. 1992;39:291-350
1475365
Behav Brain Res. 2008 Nov 3;193(1):1-16
18571741
Am J Med. 2008 Apr;121(4 Suppl 1):S3-10
18342164
J Neurosci. 2002 May 15;22(10):RC222
12006604
J Psychiatry Neurosci. 2009 Mar;34(2):88-101
19270759
Genomics. 1992 Dec;14(4):1104-6
1478653
Nicotine Tob Res. 2003 Oct;5(5):635-44
14577980
CNS Drugs. 2009 Aug;23(8):661-8
19594195
Neuropsychopharmacology. 2008 Feb;33(3):588-98
17443125
J Clin Exp Neuropsychol. 2006 Feb;28(2):193-207
16484093
Psychopharmacology (Berl). 1984;84(1):5-11
6436890
Psychopharmacology (Berl). 1998 Nov;140(1):38-41
9862400
Nature. 1996 Oct 24;383(6602):713-6
8878480
J Consult Clin Psychol. 2004 Apr;72(2):139-54
15065950
Alcohol Alcohol. 2007 May-Jun;42(3):258-66
17526637
Genes Brain Behav. 2009 Feb;8(1):36-42
19076243
Psychopharmacology (Berl). 2007 Feb;190(2):157-70
17115136
Neuroscience. 2007 Jul 29;147(4):974-85
17590520
Neuron. 2002 Oct 24;36(3):539-48
12408855
Arch Gen Psychiatry. 2005 Jun;62(6):649-59
15939842
J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2008 Nov;194(11):957-62
18797877
Am J Hum Genet. 2004 Jul;75(1):112-21
15154117
Nicotine Tob Res. 2007 Nov;9 Suppl 4:S523-36
18067030
Behav Pharmacol. 2006 Dec;17(8):731-5
17110799
J Chem Neuroanat. 1992 Sep-Oct;5(5):399-405
1418753
Behav Brain Res. 2000 Aug;113(1-2):97-103
10942036
Hum Mol Genet. 2003 Feb 1;12(3):205-16
12554675
Biochemistry. 1995 Apr 4;34(13):4202-10
7703232
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22
11381111
Pharmacol Ther. 2009 Jun;122(3):302-11
19351547
Pharmacogenomics J. 2004;4(2):102-9
14732864
Neuroscience. 2006 Aug 11;141(1):201-12
16713104
Mol Psychiatry. 1998 Sep;3(5):386-96
9774771
Biol Psychiatry. 2005 Jan 1;57(1):56-66
15607301
Curr Pharm Des. 2006;12(4):407-28
16472136
Circulation. 2005 Jul 26;112(4):489-97
16027251
Neuropharmacology. 2004;47 Suppl 1:227-41
15464140
Mol Psychiatry. 2003 Apr;8(4):393-6
12740596
Mol Psychiatry. 2002;7(9):1006-11
12399955
Psychopharmacology (Berl). 1998 Aug;138(3-4):217-30
9725745
Psychopharmacology (Berl). 1996 Sep;127(1):31-8
8880941
Mol Psychiatry. 2009 Aug;14(8):820-6
19065145
J Pharmacol Exp Ther. 1969 Dec;170(2):221-31
4982310
Addict Biol. 2008 Sep;13(3-4):435-9
18331372
Addict Behav. 2004 Sep;29(7):1275-94
15345265
Exp Brain Res. 2009 Jul;196(3):467-74
19484465
Mol Psychiatry. 2004 Dec;9(12):1060-1
15278099
Nature. 1995 Mar 2;374(6517):65-7
7870173
Nature. 1991 Apr 18;350(6319):610-4
1840645
Eur J Clin Pharmacol. 2002 Aug;58(5):309-14
12185553
J Neurosci. 2008 Nov 19;28(47):12465-76
19020039
Neurosci Lett. 2006 Dec 13;410(1):15-9
17055644
Nature. 2008 Apr 3;452(7187):638-642
18385739
Neuropsychopharmacology. 1996 Aug;15(2):152-62
8840351
Pharmacogenet Genomics. 2007 Oct;17(10):867-72
17885625
Exp Brain Res. 2005 Jan;160(1):60-70
15480606
Science. 1978 Dec 1;202(4371):939-48
568822
Brain Res. 1994 Aug 8;653(1-2):278-84
7982062
Psychopharmacology (Berl). 1990;100(4):535-41
2320715
Behav Pharmacol. 2000 Nov;11(7-8):621-9
11198133
Epilepsy Res. 2009 Feb;83(2-3):152-6
19058950
Schizophr Res. 2008 Oct;105(1-3):156-64
18718740
Neuropsychopharmacology. 2001 Sep;25(3):313-9
11522460
Med Clin North Am. 1992 Mar;76(2):399-414
1548968
Physiol Rev. 1998 Jan;78(1):189-225
9457173
Arch Gen Psychiatry. 2006 Jun;63(6):630-8
16754836
Neuropsychobiology. 1983;9(4):223-9
6646394
Neuropsychopharmacology. 2007 Dec;32(12):2465-78
17375139
Genes Brain Behav. 2009 Feb;8(1):86-96
19220487
Psychopharmacology (Berl). 2006 Dec;189(2):211-23
17019565
Int Rev Neurobiol. 2007;78:225-46
17349863
Neurobiol Aging. 2008 Jul;29(7):1123-5
17353070
Prog Neurobiol. 1997 Oct;53(2):199-237
9364611
J Abnorm Psychol. 2002 Feb;111(1):134-43
11866166
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7673-5
10884398
Nicotine Tob Res. 2004 Apr;6(2):249-67
15203798
Am J Med Genet. 2002 Dec 8;114(8):975-9
12457396
Int J Tuberc Lung Dis. 2003 Sep;7(9):811-9
12971663
Behav Genet. 2008 Sep;38(5):503-14
18607712
Tob Control. 2007 Apr;16(2):138-42
17400953
Brain Res. 1994 May 9;645(1-2):309-17
8062092
Cell Mol Neurobiol. 2007 Aug;27(5):609-39
17554626
Behav Brain Res. 2000 Aug;113(1-2):169-81
10942043
Psychopharmacology (Berl). 2006 Nov;188(4):530-40
16896957
J Neurosci. 1993 Feb;13(2):596-604
7678857
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7699-704
9636213
Biol Psychiatry. 2005 Jul 15;58(2):143-50
16038685
Trends Pharmacol Sci. 1995 Aug;16(8):270-5
7482988
Psychopharmacology (Berl). 1984;84(2):231-6
6438682
Biol Psychiatry. 2001 Oct 1;50(7):493-500
11600102
JAMA. 2002 Oct 9;288(14):1768-71
12365962
Arch Gen Psychiatry. 2003 Sep;60(9):889-96
12963670
Biol Psychiatry. 2001 Sep 15;50(6):441-6
11566161
Cancer Res. 2009 Sep 1;69(17):6848-56
19706762