, Volume 184, Issue 3–4, pp 274–285 | Cite as

Nicotine and nonnicotine factors in cigarette addiction

  • Jed E. Rose



A great deal of research supports the role of nicotine in cigarette addiction. However, the effectiveness of nicotine replacement therapy (NRT) as a smoking cessation treatment has fallen short of initial hopes. A key reason may be that NRT does not address nonnicotine components of smoking reinforcement. These include constituents that provide reinforcing sensory stimulation, components that minimize excessive irritation from inhaled nicotine and other pharmacologically active compounds in cigarette smoke.


Studies using various paradigms to dissociate nicotine from other components of smoking are summarized.


Nonnicotine components provide many rewarding effects, often surpassing the direct effects of nicotine. Substitutes for the sensory effects of smoking may be effective in relieving craving for cigarettes and in facilitating smoking cessation. Moreover, techniques for devaluing smoking-related cues may decrease craving and enhance subsequent abstinence. Promising approaches for devaluing smoke cues include extinction-based treatments employing denicotinized cigarettes and the use of nicotinic agonist and/or antagonist treatment during the weeks leading up to a quit attempt. Recent studies suggest that incorporating these approaches into a treatment program may significantly increase smoking abstinence rates. Preliminary findings also suggest that replacement of the effects of monoamine oxidase inhibitors contained in cigarette smoke may enhance quit rates.


While current NRT methods have been the mainstay of smoking cessation treatment and will likely continue to serve a useful role, the next stage of progress will likely entail the development of tools designed with recognition of the importance of nonnicotine components of cigarette smoking.


Addiction Cigarette Smoking cessation Sensory Reinforcement Nicotine Conditioning Antagonist 



Support was provided by a grant from Philip Morris USA, Inc.


  1. Alimohammadi H, Silver WL (2000) Evidence for nicotinic acetylcholine receptors on nasal trigeminal nerve endings of the rat. Chem Senses 25:61–66CrossRefPubMedGoogle Scholar
  2. Baker RR, Pereira da Silva JR, Smith G (2004) The effect of tobacco ingredients on smoke chemistry. Part I: Flavourings and additives. Food Chem Toxicol 42(Suppl):S3–S37CrossRefPubMedGoogle Scholar
  3. Baldinger B, Hasenfratz M, Battig K (1995) Comparison of the effects of nicotine on a fixed rate and a subject-paced version of the rapid information processing task. Psychopharmacology (Berl) 121:396–400CrossRefGoogle Scholar
  4. Balfour DJ, Wright AE, Benwell ME, Birrell CE (2000) The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 113:73–83CrossRefPubMedGoogle Scholar
  5. Behm FM, Rose JE (1994) Reducing craving for cigarettes while decreasing smoke intake using capsaicin-enhanced low-tar cigarettes. Exp Clin Psychopharmacol 2:143–153CrossRefGoogle Scholar
  6. Behm FM, Levin ED, Lee YK, Rose JE (1990) Low-nicotine smoke aerosol reduces desire for cigarettes. J Subst Abuse 2:237–247PubMedGoogle Scholar
  7. Behm FM, Schur C, Levin ED, Tashkin DP, Rose JE (1993) Clinical evaluation of a citric acid inhaler for smoking cessation. Drug Alcohol Depend 31:131–138CrossRefPubMedGoogle Scholar
  8. Belluzzi JD, Wang R, Leslie FM (2005) Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705–712CrossRefPubMedGoogle Scholar
  9. Benowitz NL, Hall SM, Herning RI, Jacob P III, Jones RT, Osman AL (1983) Smokers of low-yield cigarettes do not consume less nicotine. N Engl J Med 309:139–142PubMedGoogle Scholar
  10. Benowitz NL, Jacob P III (1990) Intravenous nicotine replacement suppresses nicotine intake from cigarette smoking. J Pharmacol Exp Ther 254:1000–1005PubMedGoogle Scholar
  11. Berlin I, Said S, Spreux-Varoquaux O, Launay JM, Olivares R, Millet V, Lecrubier Y, Puech AJ (1995) A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers. Clin Pharmacol Ther 58:444–452CrossRefPubMedGoogle Scholar
  12. Bohadana A, Nilsson F, Rasmussen T, Martinet Y (2000) Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 160:3128–3134CrossRefPubMedGoogle Scholar
  13. Bouton ME, King DA (1983) Contextual control of the extinction of conditioned fear: tests for the associative value of the context. J Exp Psychol Anim Behav Process 9:248–265PubMedGoogle Scholar
  14. Brauer LH, Behm FM, Lane JD, Westman EC, Perkins C, Rose JE (2001a) Individual differences in smoking reward from de-nicotinized cigarettes. Nicotine Tob Res 3:101–109CrossRefGoogle Scholar
  15. Brauer LH, Cramblett MJ, Paxton DA, Rose JE (2001b) Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes. Psychopharmacology (Berl) 159:31–37CrossRefGoogle Scholar
  16. Breland AB, Evans SE, Buchhalter AR, Eissenberg T (2002) Acute effects of Advance: a potential reduced exposure product for smokers. Tob Control 11:376–378CrossRefPubMedGoogle Scholar
  17. Brewer BG, Roberts AM, Rowell PP (2004) Short-term distribution of nicotine in the rat lung. Drug Alcohol Depend 75:193–198CrossRefPubMedGoogle Scholar
  18. Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, Hahn EL, Mandelkern MA (2004) Smoking-induced ventral striatum dopamine release. Am J Psychiatry 161:1211–1218CrossRefPubMedGoogle Scholar
  19. Buchhalter AR, Acosta MC, Evans SE, Breland AB, Eissenberg T (2005) Tobacco abstinence symptom suppression: the role played by the smoking-related stimuli that are delivered by denicotinized cigarettes. Addiction 100:550–559CrossRefPubMedGoogle Scholar
  20. Butschky MF, Bailey D, Henningfield JE, Pickworth WB (1995) Smoking without nicotine delivery decreases withdrawal in 12-hour abstinent smokers. Pharmacol Biochem Behav 50:91–96CrossRefPubMedGoogle Scholar
  21. Caggiula AR, Donny EC, Chaudhri N, Perkins KA, Evans-Martin FF, Sved AF (2002) Importance of nonpharmacological factors in nicotine self-administration. Physiol Behav 77:683–687CrossRefPubMedGoogle Scholar
  22. Cardinal RN, Everitt BJ (2004) Neural and psychological mechanisms underlying appetitive learning: links to drug addiction. Curr Opin Neurobiol 14:156–162CrossRefPubMedGoogle Scholar
  23. Caskey NH, Jarvik ME, Wirshing WC, Madsen DC, Iwamoto-Schaap PN, Eisenberger NI, Huerta L, Terrace SM, Olmstead RE (2002) Modulating tobacco smoking rates by dopaminergic stimulation and blockade. Nicotine Tob Res 4:259–266CrossRefPubMedGoogle Scholar
  24. Conkling MA, Song W, Mendu N (2002) Regulation of quinolate phosphoribosyl transferase expression. US Patent No. 6423520Google Scholar
  25. Corrigall WA, Franklin KB, Coen KM, Clarke PB (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology (Berl) 107:285–289CrossRefGoogle Scholar
  26. Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL, Mailliard JA, Ebbert LP, Swan DK, Walsh DJ, Wiesenfeld M, Levitt R, Stella P, Johnson PA, Tschetter LK, Loprinzi C (2003) Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Nicotine Tob Res 5:181–187PubMedGoogle Scholar
  27. Dallery J, Houtsmuller EJ, Pickworth WB, Stitzer ML (2003) Effects of cigarette nicotine content and smoking pace on subsequent craving and smoking. Psychopharmacology (Berl) 165:172–180Google Scholar
  28. Dawe S, Gerada C, Russell MA, Gray JA (1995) Nicotine intake in smokers increases following a single dose of haloperidol. Psychopharmacology (Berl) 117:110–115CrossRefGoogle Scholar
  29. Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314CrossRefPubMedGoogle Scholar
  30. Donny EC, Chaudhri N, Caggiula AR, Evans-Martin FF, Booth S, Gharib MA, Clements LA, Sved AF (2003) Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement. Psychopharmacology (Berl) 169:68–76CrossRefGoogle Scholar
  31. Ferguson DG, Haxhiu MA, To AJ, Erokwu B, Dreshaj IA (2000) The alpha3 subtype of the nicotinic acetylcholine receptor is expressed in airway-related neurons of the nucleus tractus solitarius, but is not essential for reflex bronchoconstriction in ferrets. Neurosci Lett 287:141–145CrossRefPubMedGoogle Scholar
  32. Ferris Wayne G, Connolly GN (2004) Application, function, and effects of menthol in cigarettes: a survey of tobacco industry documents. Nicotine Tob Res 6(Suppl 1):S43–S54CrossRefPubMedGoogle Scholar
  33. Fiore MC, Bailey WC, Cohen SJ, Dorfman SF, Goldstein MG, Gritz ER, Heyman RB, Jaen CR, Kottke TE, Lando HA, Mecklenburg R, Mullen PD, Nett LM, Robinson L, Stitzer ML, Tommasello AC, Villejo L, Wewers ME (2000) Treating tobacco use and dependence. Clinical practice guideline. US Department of Health and Human Services, Public Health Service, Rockville, MAGoogle Scholar
  34. Fowler JS, Volkow ND, Wang G-J, Pappas N, Logan J, MacGregor RR, Alexoff D, Shea C, Schlyer DJ, Wolf AP, Warner D, Zezulkova I, Cilento R (1996a) Inhibition of monoamine oxidase B in the brains of smokers. Nature 379:732–736CrossRefGoogle Scholar
  35. Fowler JS, Volkow ND, Wang G-J, Pappas N, Logan J, Shea C, Alexoff D, MacGregor RR, Schlyer DJ, Zezulkova I, Wolf AP (1996b) Brain monoamine oxidase A inhibition in cigarette smokers. Proc Natl Acad Sci U S A 93:14065–14069CrossRefGoogle Scholar
  36. Galeotti N, Ghelardini C, Mannelli L, Mazzanti G, Baghiroli L, Bartolini A (2001) Local anaesthetic activity of (+)- and (−)-menthol. Planta Med 67:174–176CrossRefPubMedGoogle Scholar
  37. Gaworski CL, Heck JD, Bennett MB, Wenk ML (1999) Toxicologic evaluation of flavor ingredients added to cigarette tobacco: skin painting bioassay of cigarette smoke condensate in SENCAR mice. Toxicology 139:1–17CrossRefPubMedGoogle Scholar
  38. George TP, Vessicchio JC, Termine A, Jatlow PI, Kosten TR, O’Malley SS (2003) A preliminary placebo-controlled trial of selegiline hydrochloride for smoking cessation. Biol Psychiatry 53:136–143CrossRefPubMedGoogle Scholar
  39. Ginzel KH, Eldred E (1977) Reflex depression of somatic motor activity from heart, lungs and carotid sinus. In: Paintal AS, Gill-Kumar P (eds) Krogh centenary symposium on respiratory adaptation, capillary exchange and reflex mechanisms. Vallabhbai Patel Chest Institute, University of Delhi, Delhi, pp 358–395Google Scholar
  40. Gross J, Lee J, Stitzer ML (1997) Nicotine-containing versus de-nicotinized cigarettes: effects on craving and withdrawal. Pharmacol Biochem Behav 57:159–165CrossRefPubMedGoogle Scholar
  41. Guillem K, Vouillac C, Azar MR, Parsons LH, Koob GF, Cador M, Stinus L (2005) Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats. J Neurosci 25:8593–8600CrossRefPubMedGoogle Scholar
  42. Hajek P, Stead LF (2004) Aversive smoking for smoking cessation. Cochrane Database Syst Rev: CD000546Google Scholar
  43. Henningfield JE, Goldberg SR (1983) Control of behavior by intravenous nicotine injections in human subjects. Pharmacol Biochem Behav 19:1021–1026CrossRefPubMedGoogle Scholar
  44. Henningfield JE, Miyasato K, Jasinski DR (1985) Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine. J Pharmacol Exp Ther 234:1–12PubMedGoogle Scholar
  45. Henningfield J, Pankow J, Garrett B (2004) Ammonia and other chemical base tobacco additives and cigarette nicotine delivery: issues and research needs. Nicotine Tob Res 6:199–205CrossRefPubMedGoogle Scholar
  46. Herning RI, Jones RT, Bachman J, Mines AH (1981) Puff volume increases when low-nicotine cigarettes are smoked. Br Med J (Clin Res Ed) 283:187–189Google Scholar
  47. Herxheimer A (1967) Circulatory effects of nicotine aerosol inhalations and cigarette smoking in man. Lancet 2:754–755CrossRefPubMedGoogle Scholar
  48. Houtsmuller EJ, Henningfield JE, Stitzer ML (2003) Subjective effects of the nicotine lozenge: assessment of abuse liability. Psychopharmacology (Berl) 167:20–27Google Scholar
  49. Jones S, Lo H, Simon SA (2002) Nicotinic receptors in the periphery. In: Levin ED (ed) Nicotinic receptors in the nervous system. CRC Press, Boca Raton, FL, pp 81–109Google Scholar
  50. Kao YR, Lee LY (1991) Mechanisms of cigarette smoke-induced stimulation of rapidly adapting receptors in canine lungs. Res Physiol 83:61–75CrossRefGoogle Scholar
  51. Kolonen S, Tuomisto J, Puustinen P, Airaksinen MM (1991) Smoking behavior in low-yield cigarette smokers and switchers in the natural environment. Pharmacol Biochem Behav 40:177–180CrossRefPubMedGoogle Scholar
  52. Kozlowski LT, Pope MA, Lux JE (1988) Prevalence of the misuse of ultra-low-tar cigarettes by blocking filter vents. Am J Public Health 78:694–695PubMedGoogle Scholar
  53. Kumar R, Cooke EC, Lader MH, Russell MA (1977) Is nicotine important to tobacco smoking? Clin Pharmacol Ther 21:520–529PubMedGoogle Scholar
  54. Kumari V, Postma P (2005) Nicotine use in schizophrenia: the self medication hypotheses. Neurosci Biobehav Rev 29:1021–1034CrossRefPubMedGoogle Scholar
  55. Lee L-Y, Gerhardstein DC, Wang AL, Burki NK (1993) Nicotine is responsible for the airway irritation evoked by cigarette smoke inhalation in men. J Appl Physiol 75:1955–1961PubMedGoogle Scholar
  56. Leonard S, Adams C, Breese CR, Adler LE, Bickford P, Byerley W, Coon H, Griffith JM, Miller C, Myles-Worsley M, Nagamoto HT, Rollins Y, Stevens KE, Waldo M, Freedman R (1996) Nicotinic receptor function in schizophrenia. Schizophr Bull 22:431–445PubMedGoogle Scholar
  57. Lerman C, Patterson F, Berrettini W (2005) Treating tobacco dependence: state of the science and new directions. J Clin Oncol 23:311–323CrossRefPubMedGoogle Scholar
  58. Levin ED, Rose JE, Behm F (1989) Controlling puff volume without disrupting smoking topography. Behav Res Methods Instrum Comput 21:383–386Google Scholar
  59. Levin ED, Behm FM, Rose JE (1990) Development of a citric acid aerosol as a smoking cessation aid. Drug Alcohol Depend 25:273–279CrossRefPubMedGoogle Scholar
  60. Levin ED, Behm FM, Carnahan E, LeClair R, Shipley R, Rose JE (1993) Clinical trials using ascorbic acid aerosol to aid smoking cessation. Drug Alcohol Depend 33:211–223CrossRefPubMedGoogle Scholar
  61. Levin ED, Westman EC, Stein RM, Carnahan E, Sanchez M, Herman S, Behm FM, Rose JE (1994) Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking. J Clin Psychopharmacol 14:41–49PubMedGoogle Scholar
  62. Lichtenstein E (2002) From rapid smoking to the internet: five decades of cessation research. Nicotine Tob Res 4:139–145CrossRefPubMedGoogle Scholar
  63. Lippiello PM, Fernandes KG (1986) The binding of l-[3H]nicotine to a single class of high affinity sites in rat brain membranes. Mol Pharmacol 29:448–454PubMedGoogle Scholar
  64. Lucchesi BR, Schuster CR, Emley GS (1967) The role of nicotine as a determinant of cigarette smoking frequency in man with observations of certain cardiovascular effects associated with the tobacco alkaloid. Clin Pharmacol Ther 8:789–796PubMedGoogle Scholar
  65. Lux JE, Frecker RC (1988) Generation of a submicrometre nicotine aerosol for inhalation. Med Biol Eng Comput 26:232–234PubMedGoogle Scholar
  66. Nil R, Battig K (1989) Separate effects of cigarette smoke yield and smoke taste on smoking behavior. Psychopharmacology 99:54–59CrossRefPubMedGoogle Scholar
  67. Pavlov IP (1927) Conditioned reflexes. Oxford University Press, OxfordGoogle Scholar
  68. Perkins KA, Gerlach D, Vender J, Grobe J, Meeker J, Hutchison S (2001) Sex differences in the subjective and reinforcing effects of visual and olfactory cigarette smoke stimuli. Nicotine Tob Res 3:141–150CrossRefPubMedGoogle Scholar
  69. Pich EM, Pagliusi SR, Tessari M, Talabot-Ayer D, Hooft van Huijsduijnen R, Chiamulera C (1997) Common neural substrates for the addictive properties of nicotine and cocaine. Science 275:83–86CrossRefPubMedGoogle Scholar
  70. Pickworth WB, Fant RV, Nelson RA, Rohrer MS, Henningfield JE (1999) Pharmacodynamic effects of new de-nicotinized cigarettes. Nicotine Tob Res 1:357–364CrossRefPubMedGoogle Scholar
  71. Pidoplichko VI, Noguchi J, Areola OO, Liang Y, Peterson J, Zhang T, Dani JA (2004) Nicotinic cholinergic synaptic mechanisms in the ventral tegmental area contribute to nicotine addiction. Learn Mem 11:60–69CrossRefPubMedGoogle Scholar
  72. Pomerleau CS, Pomerleau OF, Majchrzak MJ (1987) Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level. Psychopharmacology 91:391–393CrossRefPubMedGoogle Scholar
  73. Pritchard WS, Robinson JH, Guy TD, Davis RA, Stiles ME (1996) Assessing the sensory role of nicotine in cigarette smoking. Psychopharmacology 127:55–62PubMedGoogle Scholar
  74. Robinson ML, Houtsmuller EJ, Moolchan ET, Pickworth WB (2000) Placebo cigarettes in smoking research. Exp Clin Psychopharmacol 3:326–332Google Scholar
  75. Robinson TE, Berridge KC (2001) Incentive-sensitization and addiction. Addiction 96:103–114CrossRefPubMedGoogle Scholar
  76. Rose JE, Behm FM (1987) Refined cigarette smoke as a method for reducing nicotine intake. Pharmacol Biochem Behav 28:305–310CrossRefPubMedGoogle Scholar
  77. Rose JE, Behm FM (1991) Psychophysiological interactions between caffeine and nicotine. Pharmacol Biochem Behav 38:333–337CrossRefPubMedGoogle Scholar
  78. Rose JE, Behm FM (1994) Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms. Drug Alcohol Depend 34:225–229CrossRefPubMedGoogle Scholar
  79. Rose J, Behm F (2004a) Effects of low nicotine content cigarettes on smoke intake. Nicotine Tob Res 6:309–319CrossRefGoogle Scholar
  80. Rose JE, Behm FM (2004b) Extinguishing the rewarding value of smoke cues: pharmacologic and behavioral treatments. Nicotine Tob Res 6:523–532CrossRefGoogle Scholar
  81. Rose JE, Hickman CS (1987) Citric acid aerosol as a potential smoking cessation aid. Chest 92:1005–1008PubMedGoogle Scholar
  82. Rose JE, Levin ED (1991a) Concurrent agonist–antagonist administration for the analysis and treatment of drug dependence. Pharmacol Biochem Behav 41:219–226CrossRefGoogle Scholar
  83. Rose JE, Levin ED (1991b) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609CrossRefGoogle Scholar
  84. Rose JE, Zinser MC, Tashkin DP, Newcomb R, Ertle A (1984) Subjective response to cigarette smoking following airway anesthetization. Addict Behav 9:211–215CrossRefPubMedGoogle Scholar
  85. Rose JE, Tashkin DP, Ertle A, Zinser MC, Lafer R (1985) Sensory blockade of smoking satisfaction. Pharmacol Biochem Behav 23:289–293CrossRefPubMedGoogle Scholar
  86. Rose JE, Sampson A, Levin ED, Henningfield JE (1988) Mecamylamine increases nicotine preference and attenuates nicotine discrimination. Pharmacol Biochem Behav 32:933–938CrossRefGoogle Scholar
  87. Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV (1994) Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Clin Pharmacol Ther 56:86–99PubMedGoogle Scholar
  88. Rose JE, Behm FM, Westman EC (1998) Nicotine–mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol 6:331–343CrossRefPubMedGoogle Scholar
  89. Rose JE, Behm FM, Westman EC, Coleman RE (1999) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend 56:99–107CrossRefPubMedGoogle Scholar
  90. Rose JE, Westman EC, Behm FM, Johnson MP, Goldberg JS (1999) Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan. Pharmacol Biochem Behav 62:165–172CrossRefPubMedGoogle Scholar
  91. Rose JE, Behm FM, Westman EC, Johnson M (2000) Dissociating nicotine and non-nicotine components of cigarette smoking. Pharmacol Biochem Behav 67:71–81CrossRefPubMedGoogle Scholar
  92. Rose JE, Behm FM, Ramsey C, Ritchie JC Jr (2001) Platelet monoamine oxidase, smoking cessation and tobacco withdrawal symptoms. Nicotine Tob Res 3:383–390CrossRefPubMedGoogle Scholar
  93. Rose JE, Behm FM, Westman EC, Bates JE, Salley A (2003) Pharmacologic and sensorimotor components of satiation in cigarette smoking. Pharmacol Biochem Behav 76:243–250CrossRefPubMedGoogle Scholar
  94. Rose JE, Behm FM, Westman EC, Kukovich P (in press) Pre-cessation treatment with nicotine skin patch facilitates smoking cessation. Nicotine Tob ResGoogle Scholar
  95. Schuurmans MM, Diacon AH, van Biljon X, Bolliger CT (2004) Effect of pre-treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial. Addiction 99:634–640CrossRefPubMedGoogle Scholar
  96. Shojaei AH, Khan M, Lim G, Khosravan R (1999) Transbuccal permeation of a nucleoside analog, dideoxycytidine: effects of menthol as a permeation enhancer. Int J Pharm 192:139–146CrossRefPubMedGoogle Scholar
  97. Stapleton JA, Russell MA, Feyerabend C, Wiseman SM, Gustavsson G, Sawe U, Wiseman D (1995) Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Addiction 90:31–42CrossRefPubMedGoogle Scholar
  98. Stolerman IP, Goldfarb T, Fink R, Jarvik ME (1973) Influencing cigarette smoking with nicotine antagonists. Psychopharmacology 28:247–259CrossRefGoogle Scholar
  99. Undem BJ, Carr MJ (2001) Pharmacology of airway afferent nerve activity. Respir Res 2:234–244CrossRefPubMedGoogle Scholar
  100. US Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction. A report of the surgeon general. US Department of Health and Human Services, Public Health Service, Center for Disease Control, Office on Smoking and Health, Rockville, MAGoogle Scholar
  101. Webster JC, Francis MM, Porter JK, Robinson G, Stokes C, Horenstein B, Papke RL (1999) Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain. Br J Pharmacol 127:1337–1348CrossRefPubMedGoogle Scholar
  102. Westman EC, Behm FM, Rose JE (1995) Airway sensory replacement combined with nicotine replacement for smoking cessation: a randomized, placebo controlled trial using a citric acid inhaler. Chest 107:1358–1364PubMedGoogle Scholar
  103. Westman EC, Behm FM, Rose JE (1996) Dissociating the nicotine and airway sensory effects of smoking. Pharmacol Biochem Behav 53:309–315CrossRefPubMedGoogle Scholar
  104. Wyvell CL, Berridge KC (2001) Incentive sensitization by previous amphetamine exposure: increased cue-triggered “wanting” for sucrose reward. J Neurosci 21:7831–7840PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Center for Nicotine and Smoking Cessation ResearchDuke University Medical CenterDurhamUSA

Personalised recommendations