, Volume 210, Issue 1, pp 1–12 | Cite as

Reinforcing effects of nicotine and non-nicotine components of cigarette smoke

  • Jed E. RoseEmail author
  • Al Salley
  • Frederique M. Behm
  • James E. Bates
  • Eric C. Westman
Original Investigation



Nicotine and non-nicotine components of cigarette smoke contribute to its reinforcing effects; however, the specific role of each component in maintaining behavior has not yet been elucidated.


To assess the reinforcing effects of nicotine and non-nicotine components of cigarette smoke by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized (“denic”) cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component.


Sixteen smokers participated in seven sessions: 1) a baseline smoking assessment, used to tailor the nicotine dose per infusion; 2) two sessions for training discrimination of IV nicotine vs. saline infusions and denic smoke vs. sham puffs; and 3) four sessions assessing choice behavior after different satiation conditions.


Denic smoke was self-administered more than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was inversely correlated with subjective ratings of “comfort” associated with nicotine. Smoke satiation reduced the number of denic puffs taken during choice periods, while prior nicotine administration did not affect puffing behavior. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke.


In established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non-nicotine factors.


Nicotine Addiction Reinforcement Self-administration 



This study was supported by the National Institute on Drug Abuse grant DA02665.


  1. 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
  2. Becker KM, Rose JE, Albino AP (2008) A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation. Nicotine Tob Res 10:1139–1148CrossRefPubMedGoogle Scholar
  3. 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
  4. Behm FM, Schur C, Levin ED, Tashkin DP, Rose JE (1993) Clinical evaluation of a citric acid inhaler for smoking cessation. Drug Alc Depend 31:131–138CrossRefGoogle Scholar
  5. Benowitz NL, Porchet H, Jacob PI (1990) Pharmacokinetics, metabolism, and pharmacodynamics of nicotine. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine Psychopharmacology. Oxford University Press, Oxford, pp 112–157Google Scholar
  6. Berridge KC (2004) Motivation concepts in behavioral neuroscience. Physiol Behav 81:179–209CrossRefPubMedGoogle Scholar
  7. Brody AL, Mandelkern MA, Costello MR, Abrams AL, Scheibal D, Farahi J, London ED, Olmstead RE, Rose JE, Mukhin AG (2009) Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette. Int J Neuropsychopharmacol 12:305–316CrossRefPubMedGoogle Scholar
  8. Cabanac M (1979) Sensory pleasure. Q Rev Biol 54:1–29CrossRefPubMedGoogle Scholar
  9. Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2001) Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav 70:515–530CrossRefPubMedGoogle Scholar
  10. Cappelleri JC, Bushmakin AG, Baker CL, Merikle E, Olufade A, Gilbert DG (2007) Confirmatory factor analyses and reliability of the modified cigarette evaluation questionnaire. Addict Behav 32:912–923CrossRefPubMedGoogle Scholar
  11. Cohen J (1988) Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates, Lawrence Erlbaum AssociatesGoogle Scholar
  12. 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
  13. Dar R, Kaplan R, Shaham L, Frenk H (2007) Euphoriant effects of nicotine in smokers: fact or artifact? Psychopharmacology 191:203–210CrossRefPubMedGoogle Scholar
  14. Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314CrossRefPubMedGoogle Scholar
  15. Donny EC, Jones M (2009) Prolonged exposure to denicotinized cigarettes with or without transdermal nicotine. Drug Alcohol Depend 104:23–33CrossRefPubMedGoogle Scholar
  16. 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
  17. Donny EC, Houtsmuller E, Stitzer ML (2007) Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction 102:324–334CrossRefPubMedGoogle Scholar
  18. Fagerström KO, Kunze M, Schoberberger R et al (1996) Nicotine dependence versus smoking prevalence: comparisons among countries and categories of smokers. Tob Control 5(1):52–56CrossRefPubMedGoogle Scholar
  19. Federal Trade Commission (2000) “Tar’, Nicotine and carbon monoxide of the smoke of 1294 varieties of domestic cigarettes for the year 1998Google Scholar
  20. Fiore MC, Bailey WC, Cohen SJea (2000) Treating tobacco use and dependence: clinical practice guideline. U.S. Department of Health and Human Services. Public Health Service, U.S. Department of Health and Human Services. Public Health ServiceGoogle Scholar
  21. Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575CrossRefPubMedGoogle Scholar
  22. Harvey DM, Yasar S, Heishman SJ, Panlilio LV, Henningfield JE, Goldberg SR (2004) Nicotine serves as an effective reinforcer of intravenous drug-taking behavior in human cigarette smokers. Psychopharmacology (Berl) 175:134–142CrossRefGoogle Scholar
  23. Henningfield J, Miyasato K, Jasinski D (1983) Cigarette smokers self-administer intravenous nicotine. Pharmacol Biochem Behav 19:887–890CrossRefPubMedGoogle Scholar
  24. Hinds W, First MW, Huber GL, Shea JW (1983) A method for measuring respiratory deposition of cigarette smoke during smoking. Am Ind Hyg Assoc J 44:113–118PubMedGoogle Scholar
  25. Hughes JR, Goldstein MG, Hurt RD, Shiffman S (1999) Recent advances in the pharmacotherapy of smoking. Jama 281:72–76CrossRefPubMedGoogle Scholar
  26. Jacob P, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr 222:61–70CrossRefPubMedGoogle Scholar
  27. Jiang T, Soussignan R, Rigaud D, Martin S, Royet JP, Brondel L, Schaal B (2008) Alliesthesia to food cues: heterogeneity across stimuli and sensory modalities. Physiol Behav 95:464–470CrossRefPubMedGoogle Scholar
  28. Johnson MW, Bickel WK, Kirshenbaum AP (2004) Substitutes for tobacco smoking: a behavioral economic analysis of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes. Drug Alcohol Depend 74:253–264CrossRefPubMedGoogle Scholar
  29. LeSage MG, Keyler DE, Collins G, Pentel PR (2003) Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between continuously infused and self-administered nicotine doses and serum concentrations. Psychopharmacology (Berl) 170:278–286CrossRefGoogle Scholar
  30. 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
  31. Meyer EL, Xiao Y, Kellar KJ (2001) Agonist regulation of rat alpha 3 beta 4 nicotinic acetylcholine receptors stably expressed in human embryonic kidney 293 cells. Mol Pharmacol 60:568–576PubMedGoogle Scholar
  32. Paszkiewicz GM, Pauly JL (2008) Spectrofluorometric method for measuring tobacco smoke particulate matter on cigarette filters and Cambridge pads. Tob Control 17(Suppl 1):i53–i58CrossRefPubMedGoogle Scholar
  33. 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
  34. 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
  35. Rose JE (2006) Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology (Berl) 184:274–285CrossRefGoogle Scholar
  36. Rose JE, Hickman CS (1987) Citric acid aerosol as a potential smoking cessation aid. Chest 92:1005–1008CrossRefPubMedGoogle Scholar
  37. Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609CrossRefPubMedGoogle Scholar
  38. Rose JE, Behm FM (1995) There is more to smoking than the CNS effects of nicotine. In: Clark PBS (ed) Effects of nicotine on biological systems II. Burkhäuser Verlag, Basel, pp 9–16Google Scholar
  39. Rose JE, Behm FM (2004) Extinguishing the rewarding value of smoke cues: pharmacologic and behavioral treatments. Nicotine Tob Res 6:523–532CrossRefPubMedGoogle Scholar
  40. Rose JE, Tashkin DP, Ertle A, Zinser MC, Lafer R (1985) Sensory blockade of smoking satisfaction. Pharmacol Biochem Behav 23:289–293CrossRefPubMedGoogle Scholar
  41. Rose JE, Levin ED, Benowitz N (1993) Saliva nicotine as an index of plasma levels in nicotine skin patch users. Ther Drug Monit 15:431–435CrossRefPubMedGoogle Scholar
  42. 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
  43. Rose JE, Behm FM, Westman EC, Coleman RE (1999a) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alc Depend 56:99–107CrossRefGoogle Scholar
  44. Rose JE, Westman EC, Behm FM, Johnson MP, Goldberg JS (1999b) Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan. Pharmacol Biochem Behav 62:165–172CrossRefPubMedGoogle Scholar
  45. 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
  46. Rose JE, Behm FM, Westman EC (2001) Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking. Pharmacol Biochem Behav 68:187–197CrossRefPubMedGoogle Scholar
  47. 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
  48. Shiffman SM, Jarvik ME (1976) Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology 50:35–39CrossRefPubMedGoogle Scholar
  49. Smith MB, Brar SP, Nelson LM, Franklin GM, Cobble ND (1992) Baclofen effect on quadriceps strength in multiple sclerosis. Arch Phys Med Rehabil 73:237–240PubMedGoogle Scholar
  50. Sofuoglu M, Waters AJ, Mooney M (2008a) Modafinil and nicotine interactions in abstinent smokers. Hum Psychopharmacol 23:21–30CrossRefPubMedGoogle Scholar
  51. Sofuoglu M, Yoo S, Hill KP, Mooney M (2008b) Self-administration of intravenous nicotine in male and female cigarette smokers. Neuropsychopharmacology 33:715–720CrossRefPubMedGoogle Scholar
  52. Stevens J (1996) Applied Multivariate Statistics for the Social Sciences. Lawrence Erlbaum Associates, Lawrence Erlbaum AssociatesGoogle Scholar
  53. U.S.D.H.H.S. (1988) The health consequences of smoking: nicotine addiction. Office on Smoking and Health, Office on Smoking and HealthGoogle Scholar
  54. 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 107:1358–1364CrossRefPubMedGoogle Scholar
  55. Westman EC, Behm FM, Rose JE (1996) Dissociating the nicotine and airway sensory effects of smoking. Pharmacol Biochem Behav 53:309–315CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jed E. Rose
    • 1
    • 3
    Email author
  • Al Salley
    • 1
  • Frederique M. Behm
    • 1
  • James E. Bates
    • 1
  • Eric C. Westman
    • 2
  1. 1.Department of PsychiatryDuke University Medical CenterDurhamUSA
  2. 2.Department of MedicineDuke University Medical CenterDurhamUSA
  3. 3.Center for Nicotine and Smoking Cessation ResearchDuke University Medical CenterDurhamUSA

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