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