Abstract
An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs ) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction.
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References
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5. American Psychiatric Association, Washington
Baiamonte BA, Valenza M, Roltsch EA, Whitaker AM, Baynes BB, Sabino V, Gilpin NW (2014) Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA). Neuropharmacology 77:217–223
Bailey KR, Rustay NR, Crawley JN (2006) Behavioral phenotyping of transgenic and knockout mice: practical concerns and potential pitfalls. ILAR J 47:124–131
Bailey CD, De Biasi M, Fletcher PJ, Lambe EK (2010) The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy. J Neurosci 30:9241–9252
Baker TB, Weiss RB, Bolt D, von Niederhausern A, Fiore MC, Dunn DM, Piper ME, Matsunami N, Smith SS, Coon H, McMahon WM, Scholand MB, Singh N, Hoidal JR, Kim SY, Leppert MF, Cannon DS (2009) Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes. Nicotine Tob Res 11:785–796
Benowitz NL (2008) Neurobiology of nicotine addiction: implications for smoking cessation treatment. Am J Med 121:S3–S10
Benwell ME, Balfour DJ, Anderson JM (1988) Evidence that tobacco smoking increases the density of (-)-[3H]nicotine binding sites in human brain. J Neurochem 50:1243–1247
Bloom AJ, Martinez M, Chen LS, Bierut LJ, Murphy SE, Goate A (2013) CYP2B6 non-coding variation associated with smoking cessation is also associated with differences in allelic expression, splicing, and nicotine metabolism independent of common amino-acid changes. PLoS One 8:e79700
Booker T, Butt CM, Wehner JM, Heinemann SF, Collins AC (2007) Decreased anxiety-like behavior in beta3 nicotinic receptor subunit knockout mice. Pharmacol Biochem Behav 87:146–157
Bordia T, Hrachova M, Chin M, McIntosh JM, Quik M (2012) Varenicline is a potent partial agonist at alpha6beta2* nicotinic acetylcholine receptors in rat and monkey striatum. J Pharmacol Exp Ther 342:327–334
Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V, Tiongson E, Chefer SI, Koren AO, Mukhin AG (2006) Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry 63:907–915
Carboni E, Bortone L, Giua C, Di Chiara G (2000) Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats. Drug Alcohol Depend 58:93–102
Chen LS, Bloom AJ, Baker TB, Smith SS, Piper ME, Martinez M, Saccone N, Hatsukami D, Goate A, Bierut L (2014) Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction 109:128–137
Conti DV, Lee W, Li D, Liu J, Van Den Berg D, Thomas PD, Bergen AW, Swan GE, Tyndale RF, Benowitz NL, Lerman C (2008) Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation. Hum Mol Genet 17:2834–2848
Crawley JN (1996) Unusual behavioral phenotypes of inbred mouse strains. Trends Neurosci 19:181–182 (discussion 188–189)
Crawley JN (2008) Behavioral phenotyping strategies for mutant mice. Neuron 57:809–818
Crawley J, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ (1997) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology 132:107–124
Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23:238–245
Cui C, Booker TK, Allen RS, Grady SR, Whiteaker P, Marks MJ, Salminen O, Tritto T, Butt CM, Allen WR, Stitzel JA, McIntosh JM, Boulter J, Collins AC, Heinemann SF (2003) The beta3 nicotinic receptor subunit: a component of alpha-conotoxin MII-binding nicotinic acetylcholine receptors that modulate dopamine release and related behaviors. J Neurosci 23:11045–11053
Dani JA, De Biasi M (2013) Mesolimbic dopamine and habenulo-interpeduncular pathways in nicotine withdrawal. Cold Spring Harb perspect Med 3:012138
Dani JA, Heinemann S (1996) Molecular and cellular aspects of nicotine abuse. Neuron 16:905–908
Dao DQ, Perez EE, Teng Y, Dani JA, De Biasi M (2014) Nicotine enhances excitability of medial habenular neurons via facilitation of neurokinin signaling. J Neurosci 34:4273–4284
Dash B, Lukas RJ, Li MD (2014) A signal peptide missense mutation associated with nicotine dependence alters alpha2*-nicotinic acetylcholine receptor function. Neuropharmacology 79:715–725
Davis JA, Gould TJ (2008) Associative learning, the hippocampus, and nicotine addiction. Curr Drug Abuse Rev 1:9–19
Davis JA, Gould TJ (2009) Hippocampal nAChRs mediate nicotine withdrawal-related learning deficits. Eur Neuropsychopharmacol 19:551–561
Davis JA, James JR, Siegel SJ, Gould TJ (2005) Withdrawal from chronic nicotine administration impairs contextual fear conditioning in C57BL/6 mice. J Neurosci 25:8708–8713
De Biasi M, Dani JA (2011) Reward, addiction, withdrawal to nicotine. Annu Rev Neurosci 34:105
De Biasi M, Salas R (2008) Influence of neuronal nicotinic receptors over nicotine addiction and withdrawal. Exp Biol Med 233:917–929
Dokal I, Pagliuca A, Deenmamode M, Mufti GJ, Lewis SM (1989) Development of polycythaemia vera in a patient with myelofibrosis. Eur J Haematol 42:96–98
Exley R, Clements MA, Hartung H, McIntosh JM, Cragg SJ (2008) Alpha6-containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology 33:2158–2166
Fanselow MS, Poulos AM (2005) The neuroscience of mammalian associative learning. Annu Rev Psychol 56:207–234
Fenster CP, Whitworth TL, Sheffield EB, Quick MW, Lester RA (1999) Upregulation of surface alpha4beta2 nicotinic receptors is initiated by receptor desensitization after chronic exposure to nicotine. J Neurosci 19:4804–4814
Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ (2011) Habenular [agr] 5 nicotinic receptor subunit signalling controls nicotine intake. Nature 471:597–601
Fowler CD, Tuesta L, Kenny PJ (2013) Role of alpha5* nicotinic acetylcholine receptors in the effects of acute and chronic nicotine treatment on brain reward function in mice. Psychopharmacology 229:503–513
Frahm S, Ślimak MA, Ferrarese L, Santos-Torres J, Antolin-Fontes B, Auer S, Filkin S, Pons S, Fontaine J-F, Tsetlin V (2011) Aversion to nicotine is regulated by the balanced activity of β4 and α5 nicotinic receptor subunits in the medial habenula. Neuron 70:522–535
Furberg H, Kim Y, Dackor J, Boerwinkle E, Franceschini N, Ardissino D, Bernardinelli L, Mannucci P, Mauri F, Merlini P, Absher D, Assimes T, Fortmann S, Iribarren C, Knowles J, Quertermous T, Ferrucci L, Tanaka T, Bis J, Furberg C, Haritunians T, McKnight B, Psaty B, Taylor K, Thacker E, Almgren P, Groop L, Ladenvall C, Boehnke M, Jackson A, Mohlke K, Stringham H, Tuomilehto J, Benjamin E, Hwang S, Levy D, Preis S, Vasan R, Duan J, Gejman P, Levinson D, Sanders A, Shi J, Lips E, McKay J, Agudo A, Barzan L, Bencko V, Benhamou S, Castellsague X, Canova C, Conway D, Fabianova E, Foretova L, Janout V, Healy C, Holcátová I, Kjaerheim K, Lagiou P, Lissowska J, Lowry R, Macfarlane T, Mates D, Richiardi L, Rudnai P, Szeszenia-Dabrowska N, Zaridze D, Znaor A, Lathrop M, Brennan P, Bandinelli S, Frayling T, Guralnik J, Milaneschi Y, Perry J, Altshuler D, Elosua R, Kathiresan S, Lucas G, Melander O, O’Donnell C, Salomaa V, Schwartz S, Voight B, Penninx B, Smit J, Vogelzangs N, Boomsma D, de Geus E, Vink J, Willemsen G, Chanock S, Gu F, Hankinson S, Hunter D, Hofman A, Tiemeier H, Uitterlinden A, van Duijn C, Walter S, Chasman D, Everett B, Paré G, Ridker P, Li M, Maes H, Audrain-McGovern J, Posthuma D, Thornton L, Lerman C, Kaprio J, Rose J, Ioannidis J, Kraft P, Lin D, Sullivan P (2010) Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 42:441–447
Gangitano D, Salas R, Teng Y, Perez E, De Biasi M (2009) Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle. Genes Brain Behav 8:398–406
Geisler S, Zahm DS (2005) Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions. J Comp Neurol 490:270–294
Gentry CL, Lukas RJ (2002) Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure. Curr Drug Targets CNS Neurol Disord 1:359–385
George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O’Dell LE, Richardson HN, Koob GF (2007) CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc Natl Acad Sci USA 104:17198–17203
Gold AB, Lerman C (2012) Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes. Hum Genet 131:857–876
Gould TJ, Portugal GS, Andre JM, Tadman MP, Marks MJ, Kenney JW, Yildirim E, Adoff M (2012) The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation. Neuropharmacology 62:2118–2125
Govind AP, Vezina P, Green WN (2009) Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol 78:756–765
Grabus SD, Martin BR, Batman AM, Tyndale RF, Sellers E, Damaj MI (2005) Nicotine physical dependence and tolerance in the mouse following chronic oral administration. Psychopharmacology 178:183–192
Grady SR, Salminen O, Laverty DC, Whiteaker P, McIntosh JM, Collins AC, Marks MJ (2007) The subtypes of nicotinic acetylcholine receptors on dopaminergic terminals of mouse striatum. Biochem Pharmacol 74:1235–1246
Grady SR, Moretti M, Zoli M, Marks MJ, Zanardi A, Pucci L, Clementi F, Gotti C (2009) Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the α3β4 and α3β3β4 subtypes mediate acetylcholine release. J Neurosci 29:2272–2282
Grady SR, Drenan RM, Breining SR, Yohannes D, Wageman CR, Fedorov NB, McKinney S, Whiteaker P, Bencherif M, Lester HA, Marks MJ (2010) Structural differences determine the relative selectivity of nicotinic compounds for native alpha 4 beta 2*-, alpha 6 beta 2*-, alpha 3 beta 4*- and alpha 7-nicotine acetylcholine receptors. Neuropharmacology 58:1054–1066
Graham AW, Schultz TK, Mayo-Smith MF, Ries RK, Wilford B (2007) Principles of addiction medicine. Lippincott Williams & Wilkins, Philadelphia
Gu DF, Hinks LJ, Morton NE, Day IN (2000) The use of long PCR to confirm three common alleles at the CYP2A6 locus and the relationship between genotype and smoking habit. Ann Hum Genet 64:383–390
Hall W, Madden P, Lynskey M (2002) The genetics of tobacco use: methods, findings and policy implications. Tob Control 11:119–124
Haller G, Druley T, Vallania FL, Mitra RD, Li P, Akk G, Steinbach JH, Breslau N, Johnson E, Hatsukami D, Stitzel J, Bierut LJ, Goate AM (2012) Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence. Hum Mol Genet 21:647–655
Hartz SM, Short SE, Saccone NL, Culverhouse R, Chen L, Schwantes-An TH, Coon H, Han Y, Stephens SH, Sun J, Chen X, Ducci F, Dueker N, Franceschini N, Frank J, Geller F, Gubjartsson D, Hansel NN, Jiang C, Keskitalo-Vuokko K, Liu Z, Lyytikainen LP, Michel M, Rawal R, Rosenberger A, Scheet P, Shaffer JR, Teumer A, Thompson JR, Vink JM, Vogelzangs N, Wenzlaff AS, Wheeler W, Xiao X, Yang BZ, Aggen SH, Balmforth AJ, Baumeister SE, Beaty T, Bennett S, Bergen AW, Boyd HA, Broms U, Campbell H, Chatterjee N, Chen J, Cheng YC, Cichon S, Couper D, Cucca F, Dick DM, Foroud T, Furberg H, Giegling I, Gu F, Hall AS, Hallfors J, Han S, Hartmann AM, Hayward C, Heikkila K, Hewitt JK, Hottenga JJ, Jensen MK, Jousilahti P, Kaakinen M, Kittner SJ, Konte B, Korhonen T, Landi MT, Laatikainen T, Leppert M, Levy SM, Mathias RA, McNeil DW, Medland SE, Montgomery GW, Muley T, Murray T, Nauck M, North K, Pergadia M, Polasek O, Ramos EM, Ripatti S, Risch A, Ruczinski I, Rudan I, Salomaa V, Schlessinger D, Styrkarsdottir U, Terracciano A, Uda M, Willemsen G, Wu X, Abecasis G, Barnes K, Bickeboller H, Boerwinkle E, Boomsma DI, Caporaso N, Duan J, Edenberg HJ, Francks C, Gejman PV, Gelernter J, Grabe HJ, Hops H, Jarvelin MR, Viikari J, Kahonen M, Kendler KS, Lehtimaki T, Levinson DF, Marazita ML, Marchini J, Melbye M, Mitchell BD, Murray JC, Nothen MM, Penninx BW, Raitakari O, Rietschel M, Rujescu D, Samani NJ, Sanders AR, Schwartz AG, Shete S, Shi J, Spitz M, Stefansson K, Swan GE, Thorgeirsson T, Volzke H, Wei Q, Wichmann HE, Amos CI, Breslau N, Cannon DS, Ehringer M, Grucza R, Hatsukami D, Heath A, Johnson EO, Kaprio J, Madden P, Martin NG, Stevens VL, Stitzel JA, Weiss RB, Kraft P, Bierut LJ (2012) Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Arch Gen Psychiatry 69:854–860
Hecht SS, Hochalter JB, Villalta PW, Murphy SE (2000) 2′-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursor. Proc Natl Acad Sci USA 97:12493–12497
Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210:453–469
Henderson BJ, Srinivasan R, Nichols WA, Dilworth CN, Gutierrez DF, Mackey ED, McKinney S, Drenan RM, Richards CI, Lester HA (2014) Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors. J Gen Physiol 143:51–66
Hildebrand BE, Nomikos GG, Hertel P, Schilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779:214–225
Hong S, Jhou TC, Smith M, Saleem KS, Hikosaka O (2011) Negative reward signals from the lateral habenula to dopamine neurons are mediated by rostromedial tegmental nucleus in primates. J Neurosci 31:11457–11471
Jackson KJ, Martin BR, Changeux J-P, Damaj MI (2008) Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs. J Pharmacol Exp Ther 325:302–312
Jackson KJ, McIntosh JM, Brunzell DH, Sanjakdar SS, Damaj MI (2009) The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal. J Pharmacol Exp Ther 331:547–554
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI (2010) Role of α5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J Pharmacol Exp Ther 334:137–146
Jackson KJ, Sanjakdar SS, Muldoon PP, McIntosh JM, Damaj MI (2013) The alpha3beta4* nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the alpha5 subunit in the mouse. Neuropharmacology 70:228–235
Jalabert M, Bourdy R, Courtin J, Veinante P, Manzoni OJ, Barrot M, Georges F (2011) Neuronal circuits underlying acute morphine action on dopamine neurons. Proc Natl Acad Sci USA 108:16446–16450
Jhou TC, Fields HL, Baxter MG, Saper CB, Holland PC (2009) The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses. Neuron 61:786–800
Kaufling J, Veinante P, Pawlowski SA, Freund-Mercier MJ, Barrot M (2009) Afferents to the GABAergic tail of the ventral tegmental area in the rat. J Comp Neurol 513:597–621
Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 70:531–549
King DP, Paciga S, Pickering E, Benowitz NL, Bierut LJ, Conti DV, Kaprio J, Lerman C, Park PW (2012) Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials. Neuropsychopharmacology 37:641–650
Koob GF, Le Moal M (2008) Addiction and the brain antireward system. Annu Rev Psychol 59:29–53
Krackow S, Vannoni E, Codita A, Mohammed AH, Cirulli F, Branchi I, Alleva E, Reichelt A, Willuweit A, Voikar V, Colacicco G, Wolfer DP, Buschmann JU, Safi K, Lipp HP (2010) Consistent behavioral phenotype differences between inbred mouse strains in the intellicage. Genes Brain Behav 9:722–731
Kubota T, Nakajima-Taniguchi C, Fukuda T, Funamoto M, Maeda M, Tange E, Ueki R, Kawashima K, Hara H, Fujio Y, Azuma J (2006) CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation. Pharmacogenomics J 6:115–119
Kuryatov A, Berrettini W, Lindstrom J (2011) Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function. Mol Pharmacol 79:119–125
Lalonde R, Strazielle C (2008) Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice. J Neurosci Methods 171:48–52
Lee AM, Jepson C, Hoffmann E, Epstein L, Hawk LW, Lerman C, Tyndale RF (2007) CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol Psychiatry 62:635–641
Leeb J, Tamse A (1985) The use of calcium hydroxide in endodontic therapy. Refuat Hashinayim 3:3–12
Lessov CN, Martin NG, Statham DJ, Todorov AA, Slutske WS, Bucholz KK, Heath AC, Madden PA (2004) Defining nicotine dependence for genetic research: evidence from Australian twins. Psychol Med 34:865–879
Li MD (2008) Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Hum Genet 123:119–131
Lobb CJ, Wilson CJ, Paladini CA (2010) A dynamic role for GABA receptors on the firing pattern of midbrain dopaminergic neurons. J Neurophysiol 104:403–413
Lotfipour S, Byun JS, Leach P, Fowler CD, Murphy NP, Kenny PJ, Gould TJ, Boulter J (2013) Targeted Deletion of the Mouse α2 Nicotinic Acetylcholine Receptor Subunit Gene (Chrna2) Potentiates Nicotine-Modulated Behaviors. J Neurosci 33:7728–7741
Luo S, Kulak JM, Cartier GE, Jacobsen RB, Yoshikami D, Olivera BM, McIntosh JM (1998) alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release. J Neurosci 18:8571–8579
Malin DH, Lake JR, Carter VA, Cunningham JS, Hebert KM, Conrad DL, Wilson OB (1994) The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat. Psychopharmacology 115:180–184
Mao D, Perry DC, Yasuda RP, Wolfe BB, Kellar KJ (2008) The alpha4beta2alpha5 nicotinic cholinergic receptor in rat brain is resistant to up-regulation by nicotine in vivo. J Neurochem 104:446–456
Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825
Matsuo N, Takao K, Nakanishi K, Yamasaki N, Tanda K, Miyakawa T (2010) Behavioral profiles of three C57BL/6 substrains. Front Behav Neurosci 4:29
Morel C, Fattore L, Pons S, Hay YA, Marti F, Lambolez B, De Biasi M, Lathrop M, Fratta W, Maskos U, Faure P (2014) Nicotine consumption is regulated by a human polymorphism in dopamine neurons. Mol Psychiatry 19:930–936
Myers CS, Taylor RC, Moolchan ET, Heishman SJ (2008) Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray. Neuropsychopharmacology 33:588–598
Nugent KL, Million-Mrkva A, Backman J, Stephens SH, Reed RM, Kochunov P, Pollin TI, Shuldiner AR, Mitchell BD, Hong LE (2014) Familial aggregation of tobacco use behaviors among amish men. Nicotine Tob Res 16:923–930
O’Dell LE, Khroyan TV (2009) Rodent models of nicotine reward: what do they tell us about tobacco abuse in humans? Pharmacol Biochem Behav 91:481–488
Paolini M, De Biasi M (2011) Mechanistic insights into nicotine withdrawal. Biochem Pharmacol 82:996–1007
Pergadia ML, Heath AC, Martin NG, Madden PA (2006) Genetic analyses of DSM-IV nicotine withdrawal in adult twins. Psychol Med 36:963–972
Pergadia ML, Agrawal A, Loukola A, Montgomery GW, Broms U, Saccone SF, Wang JC, Todorov AA, Heikkila K, Statham DJ, Henders AK, Campbell MJ, Rice JP, Todd RD, Heath AC, Goate AM, Peltonen L, Kaprio J, Martin NG, Madden PA (2009) Genetic linkage findings for DSM-IV nicotine withdrawal in two populations. Am J Med Genet B Neuropsychiatr Genet 150b:950–959
Perkins KA, Lerman C, Mercincavage M, Fonte CA, Briski JL (2009) Nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene and short-term ability to quit smoking in response to nicotine patch. Cancer Epidemiol Biomarkers Prev 18:2608–2612
Perry DC, Mao D, Gold AB, McIntosh JM, Pezzullo JC, Kellar KJ (2007) Chronic nicotine differentially regulates alpha6- and beta3-containing nicotinic cholinergic receptors in rat brain. J Pharmacol Exp Ther 322:306–315
Picciotto MR, Addy NA, Mineur YS, Brunzell DH (2008) It is not “either/or”: activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog Neurobiol 84:329–342
Pietila K, Lahde T, Attila M, Ahtee L, Nordberg A (1998) Regulation of nicotinic receptors in the brain of mice withdrawn from chronic oral nicotine treatment. Naunyn Schmiedebergs Arch Pharmacol 357:176–182
Portugal GS, Wilkinson DS, Turner JR, Blendy JA, Gould TJ (2012) Developmental effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning. Neurobiol Learn Mem 97:482–494
Quick MW, Lester RA (2002) Desensitization of neuronal nicotinic receptors. J Neurobiol 53:457–478
Rada P, Jensen K, Hoebel BG (2001) Effects of nicotine and mecamylamine-induced withdrawal on extracellular dopamine and acetylcholine in the rat nucleus accumbens. Psychopharmacology 157:105–110
Rennard SI, Daughton DM (2014) Smoking cessation. Clin Chest Med 35:165–176
Rezvani K, Teng Y, Pan Y, Dani JA, Lindstrom J, Garcia Gras EA, McIntosh JM, De Biasi M (2009) UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors. J Neurosci 29:6883–6896
Rezvani K, Teng Y, De Biasi M (2010) The ubiquitin–proteasome system regulates the stability of neuronal nicotinic acetylcholine receptors. J Mol Neurosci 40:177–184
Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163:362–380
Robinson JD, Lam CY, Minnix JA, Wetter DW, Tomlinson GE, Minna JD, Chen TT, Cinciripini PM (2007) The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms. Pharmacogenomics J 7:266–274
Rogan SC, Roth BL (2011) Remote control of neuronal signaling. Pharmacol Rev 63:291–315
Saccone NL, Saccone SF, Hinrichs AL, Stitzel JA, Duan W, Pergadia ML, Agrawal A, Breslau N, Grucza RA, Hatsukami D, Johnson EO, Madden PA, Swan GE, Wang JC, Goate AM, Rice JP, Bierut LJ (2009) Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. Am J Med Genet B Neuropsychiatr Genet 150b:453–466
Salas R, Orr-Urtreger A, Broide RS, Beaudet A, Paylor R, De Biasi M (2003a) The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo. Mol Pharmacol 63:1059–1066
Salas R, Pieri F, Fung B, Dani JA, De Biasi M (2003b) Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J Neurosci 23:6255–6263
Salas R, Pieri F, De Biasi M (2004) Decreased signs of nicotine withdrawal in mice null for the β4 nicotinic acetylcholine receptor subunit. J Neurosci 24:10035–10039
Salas R, Main A, Gangitano D, De Biasi M (2007) Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the α7 nicotinic acetylcholine receptor subunit. Neuropharmacology 53:863–869
Salas R, Sturm R, Boulter J, De Biasi M (2009) Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. J Neurosci 29:3014–3018
Sallette J, Bohler S, Benoit P, Soudant M, Pons S, Le Novere N, Changeux JP, Corringer PJ (2004) An extracellular protein microdomain controls up-regulation of neuronal nicotinic acetylcholine receptors by nicotine. J Biol Chem 279:18767–18775
Sarginson JE, Killen JD, Lazzeroni LC, Fortmann SP, Ryan HS, Schatzberg AF, Murphy GM Jr (2011) Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy. Am J Med Genet B Neuropsychiatr Genet 156b:275–284
Schultz W, Tremblay L, Hollerman JR (1998) Reward prediction in primate basal ganglia and frontal cortex. Neuropharmacology 37:421–429
Shoaib M, Bizarro L (2005) Deficits in a sustained attention task following nicotine withdrawal in rats. Psychopharmacology 178:211–222
Siggens L, Ekwall K (2014) Epigenetics, chromatin and genome organization: recent advances from the ENCODE project. J Intern Med 276:201–214
Sigurdsson T, Doyere V, Cain CK, LeDoux JE (2007) Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory. Neuropharmacology 52:215–227
Smith RJ, Aston-Jones G (2008) Noradrenergic transmission in the extended amygdala: role in increased drug-seeking and relapse during protracted drug abstinence. Brain Struct Funct 213:43–61
Srinivasan R, Pantoja R, Moss FJ, Mackey ED, Son CD, Miwa J, Lester HA (2011) Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning. J Gen Physiol 137:59–79
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM (2006) Human tobacco smokers in early abstinence have higher levels of β2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci 26:8707–8714
Stoker AK, Olivier B, Markou A (2012) Role of α7-and β4-containing nicotinic acetylcholine receptors in the affective and somatic aspects of nicotine withdrawal: studies in knockout mice. Behav Genet 42:423–436
Thanos P, Delis F, Rosko L, Volkow ND (2013) Passive response to stress in adolescent female and adult male mice after intermittent nicotine exposure in adolescence. J Addict Res Ther Suppl 6:007
Thorgeirsson TE, Gudbjartsson DF, Surakka I, Vink JM, Amin N, Geller F, Sulem P, Rafnar T, Esko T, Walter S, Gieger C, Rawal R, Mangino M, Prokopenko I, Magi R, Keskitalo K, Gudjonsdottir IH, Gretarsdottir S, Stefansson H, Thompson JR, Aulchenko YS, Nelis M, Aben KK, den Heijer M, Dirksen A, Ashraf H, Soranzo N, Valdes AM, Steves C, Uitterlinden AG, Hofman A, Tonjes A, Kovacs P, Hottenga JJ, Willemsen G, Vogelzangs N, Doring A, Dahmen N, Nitz B, Pergadia ML, Saez B, De Diego V, Lezcano V, Garcia-Prats MD, Ripatti S, Perola M, Kettunen J, Hartikainen AL, Pouta A, Laitinen J, Isohanni M, Huei-Yi S, Allen M, Krestyaninova M, Hall AS, Jones GT, van Rij AM, Mueller T, Dieplinger B, Haltmayer M, Jonsson S, Matthiasson SE, Oskarsson H, Tyrfingsson T, Kiemeney LA, Mayordomo JI, Lindholt JS, Pedersen JH, Franklin WA, Wolf H, Montgomery GW, Heath AC, Martin NG, Madden PA, Giegling I, Rujescu D, Jarvelin MR, Salomaa V, Stumvoll M, Spector TD, Wichmann HE, Metspalu A, Samani NJ, Penninx BW, Oostra BA, Boomsma DI, Tiemeier H, van Duijn CM, Kaprio J, Gulcher JR, McCarthy MI, Peltonen L, Thorsteinsdottir U, Stefansson K (2010) Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nat Genet 42:448–453
Tobler PN, O’Doherty JP, Dolan RJ, Schultz W (2007) Reward value coding distinct from risk attitude-related uncertainty coding in human reward systems. J Neurophysiol 97:1621
Tumkosit P, Kuryatov A, Luo J, Lindstrom J (2006) Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines. Mol Pharmacol 70:1358–1368
Turner JR, Castellano LM, Blendy JA (2011) Parallel anxiolytic-like effects and upregulation of neuronal nicotinic acetylcholine receptors following chronic nicotine and varenicline. Nicotine Tob Res 13:41–46
Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE (2007) Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet 8:10
Ungless MA, Magill PJ, Bolam JP (2004) Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303:2040–2042
Viswanath H, Carter AQ, Baldwin PR, Molfese DL, Salas R (2013) The medial habenula: still neglected. Font Hum Neurosci 7:931
Wahlsten D (2010) Mouse behavioral testing: how to use mice in behavioral neuroscience. Academic Press, London
Wang F, Nelson ME, Kuryatov A, Olale F, Cooper J, Keyser K, Lindstrom J (1998) Chronic nicotine treatment up-regulates human alpha3 beta2 but not alpha3 beta4 acetylcholine receptors stably transfected in human embryonic kidney cells. J Biol Chem 273:28721–28732
Wang S, van der Vaart AD, Xu Q, Seneviratne C, Pomerleau OF, Pomerleau CS, Payne TJ, Ma JZ, Li MD (2014) Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations. Hum Genet 133:575–586
Wesnes KA, Edgar CJ, Kezic I, Salih HM, de Boer P (2013) Effects of nicotine withdrawal on cognition in a clinical trial setting. Psychopharmacology 229:133–140
Xian H, Scherrer JF, Madden PA, Lyons MJ, Tsuang M, True WR, Eisen SA (2003) The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit. Nicotine Tob Res 5:245–254
Xian H, Scherrer JF, Madden PA, Lyons MJ, Tsuang M, True WR, Eisen SA (2005) Latent class typology of nicotine withdrawal: genetic contributions and association with failed smoking cessation and psychiatric disorders. Psychol Med 35:409–419
Xu W, Gelber S, Orr-Urtreger A, Armstrong D, Lewis RA, Ou CN, Patrick J, Role L, De Biasi M, Beaudet AL (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 96:5746–5751
Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K (2011) Optogenetics in neural systems. Neuron 71:9–34
Zhang L, Dong Y, Doyon WM, Dani JA (2012) Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in the nucleus accumbens. Biol Psychiatry 71:184–191
Zhao-Shea R, Liu L, Soll LG, Improgo MR, Meyers EE, McIntosh JM, Grady SR, Marks MJ, Gardner PD, Tapper AR (2011) Nicotine-mediated activation of dopaminergic neurons in distinct regions of the ventral tegmental area. Neuropsychopharmacology 36:1021–1032
Zhao-Shea R, Liu L, Pang X, Gardner PD, Tapper AR (2013) Activation of GABAergic neurons in the interpeduncular nucleus triggers physical nicotine withdrawal symptoms. Curr Biol 23:2327–2335
Acknowledgments
Funding: This work was supported in part by the following NIH grants: DA024385, U19CA148127 (MDB); DA036572 (JAD & MDB) and DA009411 (JAD).
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McLaughlin, I., Dani, J.A., De Biasi, M. (2015). Nicotine Withdrawal. In: Balfour, D., Munafò, M. (eds) The Neuropharmacology of Nicotine Dependence. Current Topics in Behavioral Neurosciences, vol 24. Springer, Cham. https://doi.org/10.1007/978-3-319-13482-6_4
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