title: Unraveling the neurobiology of nicotine dependence using genetically engineered mice.
abstract: This review article provides an overview of recent studies of nicotine dependence and withdrawal that used genetically engineered mice. Major progress has been made in recent years with mutant mice that have knockout and gain-of-function of specific neuronal nicotinic acetylcholine receptor (nAChR) subunit genes. Nicotine exerts its actions by binding to neuronal nAChRs that consist of five subunits. The different nAChR subunits that combine to compose a receptor determine the distinct pharmacological and kinetic properties of the specific nAChR. Recent findings in genetically engineered mice have indicated that while α4-containing and β2-containing nAChRs are involved in the acquisition of nicotine self-administration and initial stages of nicotine dependence, α7 homomeric nAChRs appear to be involved in the later stages of nicotine dependence. In the medial habenula, α5-containing, α3-containing, and β4-containing nAChRs were shown to be crucially important in the regulation of the aversive aspects of nicotine. Studies of the involvement of α6 nAChR subunits in nicotine dependence have only recently emerged. The use of genetically engineered mice continues to vastly improve our understanding of the neurobiology of nicotine dependence and withdrawal.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093-0603, USA.
authors.forename: Astrid K
authors.initials: AK
authors.lastname: Stoker
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009446:Neurobiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic
references.citation: J Neurosci. 2004 Nov 10;24(45):10035-9
references.pmid: 15537871
references.citation: Nature. 2008 Apr 3;452(7187):633-7
references.pmid: 18385738
references.citation: Nicotine Tob Res. 2004 Feb;6(1):145-58
references.pmid: 14982698
references.citation: J Pharmacol Exp Ther. 2008 Apr;325(1):302-12
references.pmid: 18184829
references.citation: Neuropharmacology. 2012 Aug;63(2):235-41
references.pmid: 22480616
references.citation: Neuropharmacology. 2008 Jun;54(8):1223-32
references.pmid: 18452957
references.citation: Psychopharmacology (Berl). 2006 Mar;184(3-4):339-44
references.pmid: 16416156
references.citation: PLoS One. 2012;7(11):e51154
references.pmid: 23226481
references.citation: Neuropharmacology. 2012 Apr;62(5-6):1935-43
references.pmid: 22239849
references.citation: Neuron. 2011 May 12;70(3):522-35
references.pmid: 21555077
references.citation: J Neurosci. 2002 Feb 15;22(4):1208-17
references.pmid: 11850448
references.citation: Biochem Pharmacol. 2009 Oct 1;78(7):703-11
references.pmid: 19481063
references.citation: J Pharmacol Exp Ther. 2009 Nov;331(2):547-54
references.pmid: 19644040
references.citation: Neuropharmacology. 2012 Oct;63(5):863-72
references.pmid: 22727822
references.citation: Nature. 2011 Mar 31;471(7340):597-601
references.pmid: 21278726
references.citation: Hum Mol Genet. 2009 Aug 15;18(16):3125-35
references.pmid: 19443489
references.citation: J Neurosci. 2008 Nov 19;28(47):12318-27
references.pmid: 19020025
references.citation: Psychopharmacology (Berl). 2003 May;167(3):257-64
references.pmid: 12682710
references.citation: Psychopharmacology (Berl). 2006 Mar;184(3-4):456-63
references.pmid: 16463055
references.citation: Annu Rev Pharmacol Toxicol. 2007;47:699-729
references.pmid: 17009926
references.citation: J Neurochem. 2000 May;74(5):2154-66
references.pmid: 10800961
references.citation: Am J Med Genet A. 2004 Jan 1;124A(1):19-27
references.pmid: 14679582
references.citation: Neurobiol Learn Mem. 2008 Feb;89(2):106-13
references.pmid: 17584502
references.citation: Eur Neuropsychopharmacol. 2009 Aug;19(8):551-61
references.pmid: 19278836
references.citation: J Neurosci. 2009 Mar 11;29(10):3014-8
references.pmid: 19279237
references.citation: Science. 2004 Nov 5;306(5698):1029-32
references.pmid: 15528443
references.citation: Hum Mol Genet. 2007 Jan 1;16(1):36-49
references.pmid: 17135278
references.citation: Annu Rev Psychol. 2004;55:463-91
references.pmid: 14744223
references.citation: Nicotine Tob Res. 2001 Nov;3(4):361-73
references.pmid: 11694204
references.citation: Nature. 2005 Jul 7;436(7047):103-7
references.pmid: 16001069
references.citation: Neuropharmacology. 2005;49 Suppl 1:167-78
references.pmid: 16023685
references.citation: J Neurosci. 2011 Jul 27;31(30):10891-902
references.pmid: 21795541
references.citation: Behav Brain Res. 2009 Jan 23;196(2):207-13
references.pmid: 18831991
references.citation: Eur J Pharmacol. 2005 May 16;515(1-3):90-3
references.pmid: 15896732
references.citation: Psychol Rev. 2004 Jan;111(1):33-51
references.pmid: 14756584
references.citation: J Pharmacol Exp Ther. 2010 Jul;334(1):137-46
references.pmid: 20400469
references.citation: Behav Genet. 2012 May;42(3):423-36
references.pmid: 22009521
references.citation: Eur J Pharmacol. 2004 Sep 19;499(1-2):121-33
references.pmid: 15363959
references.citation: Proc Natl Acad Sci U S A. 2011 May 3;108(18):7577-82
references.pmid: 21502501
references.citation: Neuropsychopharmacology. 2011 Jun;36(7):1505-17
references.pmid: 21430644
references.citation: PLoS Genet. 2010 Aug 05;6(8):
references.pmid: 20700436
references.citation: Psychopharmacology (Berl). 1993;112(2-3):163-82
references.pmid: 7871016
references.citation: Nature. 1998 Jan 8;391(6663):173-7
references.pmid: 9428762
references.citation: Proc Natl Acad Sci U S A. 1999 May 11;96(10):5746-51
references.pmid: 10318955
references.citation: Neuropsychopharmacology. 2012 Sep;37(10):2332-44
references.pmid: 22669166
references.citation: J Neurosci. 2009 Feb 18;29(7):2272-82
references.pmid: 19228980
references.citation: Clin Cancer Res. 2009 Mar 1;15(5):1837-42
references.pmid: 19223495
references.citation: Psychopharmacology (Berl). 2012 Mar;220(1):1-14
references.pmid: 21901321
references.citation: Neuropharmacology. 2007 Dec;53(7):863-9
references.pmid: 17920082
references.citation: Psychopharmacology (Berl). 2012 May;221(2):317-27
references.pmid: 22147259
references.citation: J Neurosci. 1997 Aug 1;17(15):5747-59
references.pmid: 9221773