Tobacco smoking is the most frequent form of substance abuse. We provide a review of the neuroadaptive changes evidenced in human smokers with regard to the current neurobiological models of addiction. Addiction is thought to result from an interplay between positive and negative reinforcement. Positive reinforcing effects of the drugs are mediated by striatal dopamine release, while negative reinforcement involves the relief of withdrawal symptoms and neurobiological stress systems. In addition, drug-related stimuli are attributed with excessive motivational value and are thought to exert a control on the behavior. This mechanism plays a central role in drug maintenance and relapse. Further neuroadaptive changes associated with chronic use of the drug consist of reduced responses to natural rewards and in the activation of an antireward system, related to neurobiological stress systems. Reduced inhibitory cognitive control is believed to support the development and the maintenance of addiction. The findings observed in human nicotine dependence are generally in line with these models. The current state of the research indicates specific neuroadaptive changes associated with nicotine addiction that need to be further elucidated with regard to their role in the treatment of nicotine dependence.
References
[1]
Ray, R.; Ruparel, K.; Newberg, A.; Wileyto, E.P.; Loughead, J.W.; Divgi, C.; Blendy, J.A.; Logan, J.; Zubieta, J.K.; Lerman, C. Human mu opioid receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proc. Natl. Acad. Sci. USA？2011, 108, 9268–9273, doi:10.1073/pnas.1018699108. 21576462
[2]
The Health Consequences of Smoking: A Report of the Surgeon General; U.S. Department of Health & Human Services: Atlanta, GA, USA, 2004.
[3]
Quaak, M.; van Schayck, C.P.; Knaapen, A.M.; van Schooten, F.J. Genetic variation as a predictor of smoking cessation success. A promising preventive and intervention tool for chronic respiratory diseases? Eur. Respir. J.？2009, 33, 468–480, doi:10.1183/09031936.00056908.
[4]
Benowitz, N.L. Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. N. Engl. J. Med.？1988, 319, 1318–1330, doi:10.1056/NEJM198811173192005.
[5]
Whiting, P.J.; Lindstrom, J.M. Characterization of bovine and human neuronal nicotinic acetylcholine receptors using monoclonal antibodies. J. Neurosci.？1988, 8, 3395–3404. 3171681
[6]
Corrigall, W.; Franklin, K.; Coen, K.; Clarke, P. The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology？1992, 107, 285–289, doi:10.1007/BF02245149.
[7]
Sannerud, C.A.; Prada, J.; Goldberg, D.M.; Goldberg, S.R. The effects of sertraline on nicotine self-administration and food-maintained responding in squirrel monkeys. Eur. J. Pharmacol.？1994, 271, 461–469, doi:10.1016/0014-2999(94)90807-9.
Clarke, P.; Fu, D.; Jakubovic, A.; Fibiger, H. Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats. J. Pharmacol. Exp. Ther.？1988, 246, 701–708. 3136244
[10]
Cumming, P.; Rosa-Neto, P.; Watanabe, H.; Smith, D.; Bender, D.; Clarke, P.B.; Gjedde, A. Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain. Neuroimage？2003, 19, 1127–1136, doi:10.1016/S1053-8119(03)00079-X.
[11]
Di Chiara, G. Drug addiction as dopamine-dependent associative learning disorder. Eur. J. Pharmacol.？1999, 375, 13–30, doi:10.1016/S0014-2999(99)00372-6. 10443561
[12]
Koob, G.; LeMoal, M. Drug abuse: Hedonic homeostatic dysregulation. Science？1997, 278, 52–58, doi:10.1126/science.278.5335.52.
[13]
Diagnostic and Statistical Manual of Mental Disorders, 4th ed.; American Psychiatric Association: Washington, DC, USA, 1994.
[14]
WHO. ICD-10 Symptom Checkliste für Psychische St？rungen; Verlag Hans Huber: Bern, Switzerland, 1995.
[15]
CDC. Cigarette smoking among adults and trends in smoking cessation-united states, 2008. Morb. Mortal. Wkly. Rep.？2009, 58, 1227–1232.
[16]
Hughes, J.R.; Keely, J.; Naud, S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction？2004, 99, 29–38, doi:10.1111/j.1360-0443.2004.00540.x.
Martin-Soelch, C. Neurobiologische und neuropsychologische modelle der substanzabh？ngigkeit. Z. Neuropsychol.？2010, 21, 153–166, doi:10.1024/1016-264X/a000015.
[19]
Uhl, G.; Blum, K.; Noble, E.; Smith, S. Substance abuse vulnerability and D2 receptor genes. Trends Neurosci.？1993, 16, 83–88, doi:10.1016/0166-2236(93)90128-9.
[20]
Kendler, K.S.; Jacobson, K.C.; Prescott, C.A.; Neale, M.C. Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. Am. J. Psychiatry？2003, 160, 687–695, doi:10.1176/appi.ajp.160.4.687.
[21]
Li, M.D.; Burmeister, M. New insights into the genetics of addiction. Nat. Rev. Genet.？2009, 10, 225–231, doi:10.1038/nrg2536. 19238175
[22]
True, W.R.; Xian, H.; Scherrer, J.F.; Madden, P.A.; Bucholz, K.K.; Heath, A.C.; Eisen, S.A.; Lyons, M.J.; Goldberg, J.; Tsuang, M. Common genetic vulnerability for nicotine and alcohol dependence in men. Arch. Gen. Psychiatry？1999, 56, 655–661, doi:10.1001/archpsyc.56.7.655. 10401514
[23]
Nurco, D.N.; Kinlock, T.W.; O’Grady, K.E.; Hanlon, T.E. Early family adversity as a precursor to narcotic addiction. Drug Alcohol Depend.？1996, 43, 103–113, doi:10.1016/S0376-8716(96)01299-9.
[24]
Sinha, R. Chronic stress, drug use, and vulnerability to addiction. Ann. N. Y. Acad. Sci.？1141, 105–130.
[25]
Volkow, N.D.; Fowler, J.S.; Wang, G.J.; Swanson, J.M.; Telang, F. Dopamine in drug abuse and addiction: Results of imaging studies and treatment implications. Arch. Neurol.？2007, 64, 1575–1579, doi:10.1001/archneur.64.11.1575.
[26]
Anthony, J.C.; Petronis, K.R. Early-onset drug use and risk of later drug problems. Drug Alcohol Depend.？1995, 40, 9–15, doi:10.1016/0376-8716(95)01194-3.
[27]
Steinberg, L.; Albert, D.; Cauffman, E.; Banich, M.; Graham, S.; Woolard, J. Age differences in sensation seeking and impulsivity as indexed by behavior and self-report: Evidence for a dual systems model. Dev. Psychol.？2008, 44, 1764–1778, doi:10.1037/a0012955. 18999337
[28]
Martin-Soelch, C. Reward and Dependence; Peter Lang: Bern, Germany, 2002.
[29]
Schultz, W. Multiple reward signals in the brain. Nat. Rev. Neurosci.？2000, 1, 199–207, doi:10.1038/35044563.
[30]
Solomon, R.L. The opponent-process theory of acquired motivation: The costs of pleasure and the benefits of pain. Am. Psychol.？1980, 35, 691–712, doi:10.1037/0003-066X.35.8.691.
[31]
Koob, G.F.; Le Moal, M. Review. Neurobiological mechanisms for opponent motivational processes in addiction. Philos. Trans. R. Soc. Lond. B Biol. Sci.？2008, 363, 3113–3123, doi:10.1098/rstb.2008.0094.
[32]
Smith, R.; Aston-Jones, G. Noradrenergic transmission in the extended amygdala: Role in increased drug-seekingand relapse during protracted drug abstinence. Brain Struct. Funct.？2008, 213, 43–61, doi:10.1007/s00429-008-0191-3. 18651175
[33]
Koob, G. Neurobiological substrates for the dark side of compulsivity in addiction. Neuropharmacology？2009, 56, 18–31, doi:10.1016/j.neuropharm.2008.07.043.
[34]
Robinson, T.; Berridge, K. The psychology and neurobiology of addiction: An incentive-sensitization view. Addiction？2000, 95, 91–117.
[35]
Everitt, B.J.; Belin, D.; Economidou, D.; Pelloux, Y.; Dalley, J.W.; Robbins, T.W. Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos. Trans. R. Soc. Lond. B Biol. Sci.？2008, 363, 3125–3135, doi:10.1098/rstb.2008.0089.
[36]
Porrino, L.J.; Daunais, J.B.; Smith, H.R.; Nader, M.A. The expanding effects of cocaine: Studies in a nonhuman primate model of cocaine self-administration. Neurosci. Biobehav. Rev.？2004, 27, 813–820, doi:10.1016/j.neubiorev.2003.11.013.
[37]
Yalachkov, Y.; Kaiser, J.; Naumer, M.J. Brain regions related to tool use and action knowledge reflect nicotine dependence. J. Neurosci.？2009, 29, 4922–4929, doi:10.1523/JNEUROSCI.4891-08.2009.
[38]
Baxter, B.W.; Hinson, R.E. Is smoking automatic? Demands of smoking behavior on attentional resources. J. Abnorm. Psychol.？2001, 110, 59–66, doi:10.1037/0021-843X.110.1.59. 11261400
[39]
Field, M.; Mogg, K.; Bradley, B.P. Automaticity of smoking behavior: The relationship between dual-task performance, daily cigarette intake and subjective nicotine effects. J. Psychopharmacol.？2006, 20, 799–805, doi:10.1177/0269881106063997.
[40]
Volkow, N.D.; Wang, G.J.; Telang, F.; Fowler, J.S.; Logan, J.; Childress, A.R.; Jayne, M.; Ma, Y.; Wong, C. Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction. J. Neurosci.？2006, 26, 6583–6588, doi:10.1523/JNEUROSCI.1544-06.2006. 16775146
[41]
Wong, D.F.; Kuwabara, H.; Schretlen, D.J.; Bonson, K.R.; Zhou, Y.; Nandi, A.; Brasic, J.R.; Kimes, A.S.; Maris, M.A.; Kumar, A.; et al. Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology？2006, 31, 2716–2727, doi:10.1038/sj.npp.1301194.
[42]
Vollstadt-Klein, S.; Wichert, S.; Rabinstein, J.; Buhler, M.; Klein, O.; Ende, G.; Hermann, D.; Mann, K. Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum. Addiction？2010, 105, 1741–1749, doi:10.1111/j.1360-0443.2010.03022.x.
[43]
B？ning, J.A. Neurobiology of an addiction memory. J. Neural Transm.？2001, 108, 755–765, doi:10.1007/s007020170050. 11478425
[44]
Robbins, T.W.; Everitt, B.J. Limbic-striatal memory systems and drug addiction. Neurobiol. Learn. Mem.？2002, 78, 625–636, doi:10.1006/nlme.2002.4103.
[45]
Koob, G.F. Dynamics of neuronal circuits in addiction: Reward, antireward, and emotional memory. Pharmacopsychiatry？2009, 42, 32–41, doi:10.1055/s-0029-1216356.
[46]
Martin-Soelch, C.; Chevalley, A.F.; Künig, G.; Missimer, J.; Magyar, S.; Mino, A.; Schultz, W.; Leenders, K.L. Changes in reward-induced brain activation in opiate addicts. Eur. J. Neurosci.？2001, 14, 1360–1368, doi:10.1046/j.0953-816x.2001.01753.x.
[47]
Martin-Soelch, C.; Magyar, S.; Künig, G.; Missimer, J.; Schultz, W.; Leenders, K.L. Changes in brain activation associated with reward processing in smokers and nonsmokers: A pet study. Exp. Brain Res.？2001, 139, 278–386, doi:10.1007/s002210100751.
[48]
Martin-Soelch, C.; Missimer, J.; Leenders, K.; Schultz, W. Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers. Eur. J. Neurosci.？2003, 18, 680–688, doi:10.1046/j.1460-9568.2003.02791.x. 12911764
[49]
Martin-Soelch, C.; Kobel, M.; Stoecklin, M.; Michael, T.; Weber, S.; Krebs, B.; Opwis, K. Reduced response to reward in smokers and cannabis users. Neuropsychobiology？2009, 60, 94–103, doi:10.1159/000239685.
[50]
Bechara, A. Decision making, impulse control and loss of willpower to resist drugs: A neurocognitive perspective. Nat. Neurosci.？2005, 8, 1458–1463, doi:10.1038/nn1584.
[51]
Bechara, A. Risky business: Emotion, decision-making, and addiction. J. Gambl. Stud.？2003, 19, 23–51, doi:10.1023/A:1021223113233.
[52]
Bechara, A.; Damasio, A.R.; Damasio, H.; Anderson, S.W. Insensitivity to future consequences following damage to human prefrontal cortex. Cognition？1994, 50, 7–15, doi:10.1016/0010-0277(94)90018-3.
[53]
Feil, J.; Sheppard, D.; Fitzgerald, P.B.; Yucel, M.; Lubman, D.I.; Bradshaw, J.L. Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control. Neurosci. Biobehav. Rev.？2010.
[54]
Bayard, S.; Raffard, S.; Gely-Nargeot, M.C. Do facets of self-reported impulsivity predict decision-making under ambiguity and risk? Evidence from a community sample. Psychiatry Res.？2011, 190, 322–326, doi:10.1016/j.psychres.2011.06.013.
[55]
Goldstein, R.Z.; Craig, A.D.; Bechara, A.; Garavan, H.; Childress, A.R.; Paulus, M.P.; Volkow, N.D. The neurocircuitry of impaired insight in drug addiction. Trends Cogn. Sci.？2009, 13, 372–380, doi:10.1016/j.tics.2009.06.004. 19716751
[56]
McLennan, J.D.; Shaw, E.; Shema, S.J.; Gardner, W.P.; Pope, S.K.; Kelleher, K.J. Adolescents’ insight in heavy drinking. J. Adolesc. Health？1998, 22, 409–416, doi:10.1016/S1054-139X(97)00201-2.
[57]
Craig, A.D. How do you feel—now? The anterior insula and human awareness. Nat. Rev. Neurosci.？2009, 10, 59–70, doi:10.1038/nrn2555.
Hester, R.; Nestor, L.; Garavan, H. Impaired error awareness and anterior cingulate cortex hypoactivity in chronic cannabis users. Neuropsychopharmacology？2009, 34, 2450–2458, doi:10.1038/npp.2009.67.
[60]
Naqvi, N.H.; Rudrauf, D.; Damasio, H.; Bechara, A. Damage to the insula disrupts addiction to cigarette smoking. Science？2007, 315, 531–534, doi:10.1126/science.1135926. 17255515
[61]
Brody, A.L.; Mandelkern, M.A.; Olmstead, R.E.; Scheibal, D.; Hahn, E.; Shiraga, S.; Zamora-Paja, E.; Farahi, J.; Saxena, S.; London, E.D.; et al. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch. Gen. Psychiatry？2006, 63, 808–816, doi:10.1001/archpsyc.63.7.808.
Scott, D.J.; Domino, E.F.; Heitzeg, M.M.; Koeppe, R.A.; Ni, L.; Guthrie, S.; Zubieta, J.K. Smoking modulation of mu opioid and dopamine D2 receptor-mediated neurotransmission in humans. Neuropsychopharmacology？2007, 32, 450–457, doi:10.1038/sj.npp.1301238.
[64]
Barrett, S.P.; Boileau, I.; Okker, J.; Pihl, R.O.; Dagher, A. The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11C]raclopride. Synapse？2004, 54, 65–71, doi:10.1002/syn.20066.
[65]
Montgomery, A.J.; Lingford-Hughes, A.R.; Egerton, A.; Nutt, D.J.; Grasby, P.M. The effect of nicotine on striatal dopamine release in man: A [11C]raclopride pet study. Synapse？2007, 61, 637–645, doi:10.1002/syn.20419. 17492764
[66]
Brody, A.L.; Mandelkern, M.A.; Olmstead, R.E.; Allen-Martinez, Z.; Scheibal, D.; Abrams, A.L.; Costello, M.R.; Farahi, J.; Saxena, S.; Monterosso, J.; et al. Ventral striatal dopamine release in response to smoking a regular vs a denicotinized cigarette. Neuropsychopharmacology？2009, 34, 282–289, doi:10.1038/npp.2008.87.
Fehr, C.; Yakushev, I.; Hohmann, N.; Buchholz, H.G.; Landvogt, C.; Deckers, H.; Eberhardt, A.; Klager, M.; Smolka, M.N.; Scheurich, A.; et al. Association of low striatal dopamine D2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse. Am. J. Psychiatry？2008, 165, 507–514, doi:10.1176/appi.ajp.2007.07020352.
[69]
Brown, A.K.; Mandelkern, M.A.; Farahi, J.; Robertson, C.; Ghahremani, D.G.; Sumerel, B.; Moallem, N.; London, E.D. Sex differences in striatal dopamine D2/D3 receptor availability in smokers and non-smokers. Int. J. Neuropsychopharmacol.？2012, 15, 989–994, doi:10.1017/S1461145711001957.
[70]
Leroy, C.; Karila, L.; Martinot, J.L.; Lukasiewicz, M.; Duchesnay, E.; Comtat, C.; Dolle, F.; Benyamina, A.; Artiges, E.; Ribeiro, M.J.; et al. Striatal and extrastriatal dopamine transporter in cannabis and tobacco addiction: A high-resolution PET study. Addict. Biol.？2011, 17, 981–990. 21812871
Das, D.; Cherbuin, N.; Anstey, K.J.; Sachdev, P.S.; Easteal, S. Lifetime cigarette smoking is associated with striatal volume measures. Addict. Biol.？2012, 17, 817–825, doi:10.1111/j.1369-1600.2010.00301.x.
[74]
Gallinat, J.; Meisenzahl, E.; Jacobsen, L.K.; Kalus, P.; Bierbrauer, J.; Kienast, T.; Witthaus, H.; Leopold, K.; Seifert, F.; Schubert, F.; et al. Smoking and structural brain deficits: A volumetric mr investigation. Eur. J. Neurosci.？2006, 24, 1744–1750, doi:10.1111/j.1460-9568.2006.05050.x.
[75]
Hong, L.E.; Gu, H.; Yang, Y.; Ross, T.J.; Salmeron, B.J.; Buchholz, B.; Thaker, G.K.; Stein, E.A. Association of nicotine addiction and nicotine’s actions with separate cingulate cortex functional circuits. Arch. Gen. Psychiatry？2009, 66, 431–441, doi:10.1001/archgenpsychiatry.2009.2.
[76]
Janes, A.C.; Nickerson, L.D.; Frederick, B.; Kaufman, M.J. Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls. Drug Alcohol Depend.？2012, 125, 252–259, doi:10.1016/j.drugalcdep.2012.02.020. 22459914
[77]
Fagerstr？m, K.-O. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict. Behav.？1978, 3, 235–241, doi:10.1016/0306-4603(78)90024-2.
Bierut, L.J.; Stitzel, J.A.; Wang, J.C.; Hinrichs, A.L.; Grucza, R.A.; Xuei, X.; Saccone, N.L.; Saccone, S.F.; Bertelsen, S.; Fox, L.; et al. Variants in nicotinic receptors and risk for nicotine dependence. Am. J. Psychiatry？2008, 165, 1163–1171, doi:10.1176/appi.ajp.2008.07111711.
[80]
Sutherland, M.T.; McHugh, M.J.; Pariyadath, V.; Stein, E.A. Resting state functional connectivity in addiction: Lessons learned and a road ahead. Neuroimage？2012, 62, 2281–2295, doi:10.1016/j.neuroimage.2012.01.117.
[81]
Shiffman, S.; Balabanis, M.H.; Gwaltney, C.J.; Paty, J.A.; Gnys, M.; Kassel, J.D.; Hickcox, M.; Paton, S.M. Prediction of lapse from associations between smoking and situational antecedents assessed by ecological momentary assessment. Drug Alcohol Depend.？2007, 91, 159–168, doi:10.1016/j.drugalcdep.2007.05.017.
[82]
Powell, J.; Dawkins, L.; Davis, R.E. Smoking, reward responsiveness, and response inhibition: Tests of an incentive motivational model. Biol. Psychiatry？2002, 51, 151–163, doi:10.1016/S0006-3223(01)01208-2.
[83]
Peters, J.; Bromberg, U.; Schneider, S.; Brassen, S.; Menz, M.; Banaschewski, T.; Conrod, P.J.; Flor, H.; Gallinat, J.; Garavan, H.; et al. Lower ventral striatal activation during reward anticipation in adolescent smokers. Am. J. Psychiatry？2011, 168, 540–549, doi:10.1176/appi.ajp.2010.10071024. 21362742
[84]
Rose, E.J.; Ross, T.J.; Salmeron, B.J.; Lee, M.; Shakleya, D.M.; Huestis, M.; Stein, E.A. Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain. Biol. Psychiatry？2012, 71, 206–213, doi:10.1016/j.biopsych.2011.09.013.
[85]
David, S.P.; Munafo, M.R.; Johansen-Berg, H.; Smith, S.M.; Rogers, R.D.; Matthews, P.M.; Walton, R.T. Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: A functional magnetic resonance imaging study. Biol. Psychiatry？2005, 58, 488–494, doi:10.1016/j.biopsych.2005.04.028.
[86]
Due, D.L.; Huettel, S.A.; Hall, W.G.; Rubin, D.C. Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: Evidence from functional magnetic resonance imaging. Am. J. Psychiatry？2002, 159, 954–960, doi:10.1176/appi.ajp.159.6.954.
McClernon, F.J.; Kozink, R.V.; Lutz, A.M.; Rose, J.E. 24-h smoking abstinence potentiates fMRI-bold activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology (Berl.)？2009, 204, 25–35, doi:10.1007/s00213-008-1436-9.
[89]
Franklin, T.R.; Wang, Z.; Li, Y.; Suh, J.J.; Goldman, M.; Lohoff, F.W.; Cruz, J.; Hazan, R.; Jens, W.; Detre, J.A.; et al. Dopamine transporter genotype modulation of neural responses to smoking cues: Confirmation in a new cohort. Addict. Biol.？2011, 16, 308–322, doi:10.1111/j.1369-1600.2010.00277.x.
[90]
Franklin, T.; Wang, Z.; Suh, J.J.; Hazan, R.; Cruz, J.; Li, Y.; Goldman, M.; Detre, J.A.; O’Brien, C.P.; Childress, A.R. Effects of varenicline on smoking cue-triggered neural and craving responses. Arch. Gen. Psychiatry？2011, 68, 516–526, doi:10.1001/archgenpsychiatry.2010.190.
[91]
Kang, O.S.; Chang, D.S.; Jahng, G.H.; Kim, S.Y.; Kim, H.; Kim, J.W.; Chung, S.Y.; Yang, S.I.; Park, H.J.; Lee, H.; et al. Individual differences in smoking-related cue reactivity in smokers: An eye-tracking and fmri study. Prog. Neuropsychopharmacol. Biol. Psychiatry？2012, 38, 285–293, doi:10.1016/j.pnpbp.2012.04.013.
[92]
Freeman, T.P.; Morgan, C.J.; Beesley, T.; Curran, H.V. Drug cue induced overshadowing: Selective disruption of natural reward processing by cigarette cues amongst abstinent but not satiated smokers. Psychol. Med.？2012, 42, 161–171, doi:10.1017/S0033291711001139.
Smolka, M.N.; Buhler, M.; Klein, S.; Zimmermann, U.; Mann, K.; Heinz, A.; Braus, D.F. Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery. Psychopharmacology (Berl.)？2006, 184, 577–588, doi:10.1007/s00213-005-0080-x.
[95]
Janes, A.C.; Frederick, B.; Richardt, S.; Burbridge, C.; Merlo-Pich, E.; Renshaw, P.F.; Evins, A.E.; Fava, M.; Kaufman, M.J. Brain fmri reactivity to smoking-related images before and during extended smoking abstinence. Exp. Clin. Psychopharmacol.？2009, 17, 365–373, doi:10.1037/a0017797.
[96]
Janes, A.C.; Pizzagalli, D.A.; Richardt, S.; de, B.F.B.; Chuzi, S.; Pachas, G.; Culhane, M.A.; Holmes, A.J.; Fava, M.; Evins, A.E.; et al. Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biol. Psychiatry？2010, 67, 722–729, doi:10.1016/j.biopsych.2009.12.034.
[97]
Heishman, S.J.; Kleykamp, B.A.; Singleton, E.G. Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl.)？2010, 210, 453–469, doi:10.1007/s00213-010-1848-1.
[98]
Nestor, L.; McCabe, E.; Jones, J.; Clancy, L.; Garavan, H. Differences in “bottom-up” and “top-down” neural activity in current and former cigarette smokers: Evidence for neural substrates which may promote nicotine abstinence through increased cognitive control. Neuroimage？2011, 56, 2258–2275, doi:10.1016/j.neuroimage.2011.03.054. 21440645
Addicott, M.A.; Baranger, D.A.; Kozink, R.V.; Smoski, M.J.; Dichter, G.S.; McClernon, F.J. Smoking withdrawal is associated with increases in brain activation during decision making and reward anticipation: A preliminary study. Psychopharmacology (Berl.)？2012, 219, 563–573, doi:10.1007/s00213-011-2404-3.
[101]
Brody, A.L.; Mandelkern, M.A.; Jarvik, M.E.; Lee, G.S.; Smith, E.C.; Huang, J.C.; Bota, R.G.; Bartzokis, G.; London, E.D. Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol. Psychiatry？2004, 55, 77–84, doi:10.1016/S0006-3223(03)00610-3.
