, Volume 200, Issue 4, pp 529–544 | Cite as

Initial nicotine sensitivity in humans as a function of impulsivity

  • Kenneth A. Perkins
  • Caryn Lerman
  • Sarah B. Coddington
  • Christopher Jetton
  • Joshua L. Karelitz
  • John A. Scott
  • Annette S. Wilson
Original Investigation



Impulsivity is related to greater risk of nicotine dependence, perhaps by enhancing sensitivity to nicotine’s reinforcing and rewarding effects during initial smoking experiences.


We examined the influence of impulsivity characteristics on acute sensitivity to nicotine reward, reinforcement, and other effects in 131 young adult nonsmokers.

Materials and methods

Participants engaged in four sessions: the first three to assess dose–response effects of nasal spray nicotine (0, 5, 10 μg/kg) on reward, as well as mood, physiological, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure. Five impulsivity factors, derived from factor analysis of self-report (e.g., Barratt Impulsivity Scale, Sensation-Seeking Scale, Novelty seeking) and computer (stop–go, delay discounting, probability discounting) measures of impulsivity, were labeled “novelty seeking”, “response disinhibition”, “extraversion”, “inhibition”, and “probability/delay discounting”.


The associations of novelty seeking with nicotine reinforcement and reward tended to move in opposite directions by sex, generally being directly related in men but inversely or unrelated in women. Similarly, response disinhibition was associated with reward and some mood responses to nicotine that differed by sex. Extraversion was inversely associated with nicotine reinforcement. Characteristics loading on to the other impulsivity factors had little association with nicotine sensitivity.


These results are preliminary, but they suggest that characteristics broadly related to impulsivity, especially novelty seeking and response disinhibition, are associated with initial sensitivity to some effects of acute nicotine, including reinforcement and reward, and may do so differentially between men and women.


Nicotine Sensitivity Impulsivity Sex differences Nonsmokers Reinforcement Reward 


  1. Anthony JC, Warner LA, Kessler RC (1994) Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: basic findings from the National Comorbidity Survey. Exper Clin Psychopharmacol 2:244–268CrossRefGoogle Scholar
  2. Audrain-McGovern J, Nigg J, Perkins KA (2008) Endophenotypes for nicotine dependence risk at or before initial nicotine exposure. National Cancer Institute Monograph 22, phenotypes and endophenotypes: foundations for genetic studies of nicotine use and dependence (chapter 7). NCI, Washington DC (in press)Google Scholar
  3. Bickel WK, Odum AL, Madden GJ (1999) Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers. Psychopharmacology 146:447–454PubMedCrossRefGoogle Scholar
  4. Blendy JA, Strasser A, Walters CL, Perkins KA, Patterson F, Berkowitz R, Lerman C (2005) Reduced nicotine reward in obesity: cross comparison in human and mouse. Psychopharmacology 180:306–315PubMedCrossRefGoogle Scholar
  5. Burke JD, Loeber R, Lahey BB (2001) Which aspects of ADHD are associated with tobacco use in early adolescence. J Child Psychol Psychiatr 42:493–502CrossRefGoogle Scholar
  6. Burt RD, Dinh KT, Peterson AV, Sarason IG (2000) Predicting adolescent smoking: a prospective study of personality variables. Prev Med 30:115–125PubMedCrossRefGoogle Scholar
  7. Buss AH, Durkee A (1957) An inventory for assessing different kinds of hostility. J Consult Psychol 21(4):343–554PubMedCrossRefGoogle Scholar
  8. Campbell-Sills L, Liverant GI, Brown TA (2004) Psychometric evaluation of the Behavioral Inhibition/Behavioral Activation Scales in a large sample of outpatients with anxiety and mood disorders. Psychol Assess 16:244–254PubMedCrossRefGoogle Scholar
  9. Carver CS, White TL (1994) Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS scales. J Personal Soc Psychol 67(2):319–334CrossRefGoogle Scholar
  10. Cloninger CR, Pryzbeck TR, Svrakic DM, Wetzel RD (1994) The Temperament and Character Inventory (TCI): a guide to its development and use. Center for Psychobiology of Personality, Washington University, St. LouisGoogle Scholar
  11. Dalley JW, Mar AC, Economidou D, Robbins TW (2008) Neurobehavioral mechanisms of impulsivity: fronto–striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90:250–260PubMedCrossRefGoogle Scholar
  12. Davis BA, Clinton SM, Akil H, Becker JB (2008) The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats. Pharmacol Biochem Behav 90:331–338PubMedCrossRefGoogle Scholar
  13. deBry SC, Tiffany ST (2008) Tobacco-induced neurotoxicity of adolescent cognitive development (TINACD): a proposed model for the development of impulsivity in nicotine dependence. Nic Tobacco Res 10:11–25CrossRefGoogle Scholar
  14. deWit H, Richards JB (2004) Dual determinants of drug use in humans: reward and impulsivity. In: Bevins RA, Bardo MT (eds) Motivational factors in the etiology of drug abuse. University of Nebraska Press, Lincoln, pp 19–55Google Scholar
  15. Diergaarde L, Pattij T, Poortvliet I, Hogenboom F, deBries W, Schoffelmeer ANM, deVries TJ (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiatr 63:301–308CrossRefGoogle Scholar
  16. Doran N, Spring B, McChargue D, Pergadia M, Richmond M (2004) Impulsivity and smoking relapse. Nic Tobacco Res 6:641–647CrossRefGoogle Scholar
  17. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R, McGoey KE, Ikeda MJ (1997) Teacher ratings of attention deficit hyperactivity disorder symptoms: factor structure and normative data. Psychol Assess 9(4):436–444CrossRefGoogle Scholar
  18. Eissenberg T, Balster RL (2000) Initial tobacco use episodes in children and adolescents: current knowledge, future directions. Drug Alc Depend 59(Suppl 1):S41–60CrossRefGoogle Scholar
  19. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology 146:348–361PubMedCrossRefGoogle Scholar
  20. Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neurosci 8:1481–1489PubMedCrossRefGoogle Scholar
  21. Eysenck HJ, Eysenck BG (1968) Eysenck Personality Inventory. Educational and Industrial Testing Services, San DiegoGoogle Scholar
  22. Gehricke JG, Whalen CK, Jamner LD, Wigal TL, Steinhoff K (2006) The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: a preliminary examination. Nic Tobacco Res 8:37–47CrossRefGoogle Scholar
  23. Gervais A, O’Loughlin J, Meshefedjian G, Bancej C, Tremblay M (2006) Milestones in the natural course of onset of cigarette use among adolescents. Can Med Assoc J 175:255–261CrossRefGoogle Scholar
  24. Grobe JE, Perkins KA, Goettler-Good J, Fonte C (1998) Importance of environmental distractors in the effects of nicotine on short-term memory. Exper Clin Psychopharmacol 6:209–216CrossRefGoogle Scholar
  25. Harakeh Z, Scholte RH, deVries H, Engels RC (2006) Association between personality and adolescent smoking. Addict Behav 31:232–245PubMedCrossRefGoogle Scholar
  26. Hester RK, Brown WR (1980) Eysenck Personality Inventory: a normative study on an adult industrial population. J Clin Psychol 36(4):937–939CrossRefGoogle Scholar
  27. Howard MO, Kivlahan D, Walker RD (1997) Cloninger’s tridimensional theory of personality and psychopathology: applications to substance use disorders. J Stud Alc 58:48–66Google Scholar
  28. Hu MC, Davies M, Kandel DB (2006) Epidemiology and correlates of daily smoking and nicotine dependence among young adults in the United States. Amer J Publ Health 96:299–308CrossRefGoogle Scholar
  29. Hughes JR (1991) Distinguishing withdrawal relief and direct effects of smoking. Psychopharmacology 104:409–410PubMedCrossRefGoogle Scholar
  30. Hutchison KE, Wood MD, Swift R (1999) Personality factors moderate subjective and psychophysiological responses to d-amphetamine in humans. Exper Clin Psychopharmacol 7:493–501CrossRefGoogle Scholar
  31. Jacob P, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatography 222:61–70CrossRefGoogle Scholar
  32. Jamner LD, Shapiro D, Jarvik ME (1999) Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high but not low hostility: an ambulatory study. Exper Clin Psychopharmacol 7:454–463CrossRefGoogle Scholar
  33. Johansson C-J, Olsson P, Bende M, Carlsson T, Gunnarsson PO (1991) Absolute bioavailability of nicotine applied to different nasal regions. Eur J Clin Pharmacol 41:585–588PubMedCrossRefGoogle Scholar
  34. Kalman D, Smith SS (2005) Does nicotine do what we think it does? A meta-analytic review of the subjective effects of nicotine in nasal spray and intravenous studies with smokers and nonsmokers. Nic Tobacco Res 7:317–333CrossRefGoogle Scholar
  35. Kelly TH, Robbins G, Martin CA, Fillmore MT, Lane SD, Harrington NG, Rush CR (2006) Individual differences in drug abuse vulnerability: d-amphetamine and sensation-seeking status. Psychopharmacology 189:17–25PubMedCrossRefGoogle Scholar
  36. Kopstein AN, Crum RM, Celentano DD, Martin SS (2001) Sensation seeking needs among 8th and 11th graders: characteristics associated with cigarette and marijuana use. Drug Alc Depend 62:195–203CrossRefGoogle Scholar
  37. Kreek MJ, Nielsen DA, Butelman ER, LaForge KS (2005) Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci 8:1450–1457PubMedCrossRefGoogle Scholar
  38. Krishnan-Sarin S, Reynolds B, Duhig AM, Smith A, Liss T, McFetridge A, Cavallo DA, Carroll KM, Potenza MN (2007) Behavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers. Drug Alc Depend 88:79–82CrossRefGoogle Scholar
  39. Lane SD, Cherek DR (2001) Risk taking by adolescents with maladaptive behavior histories. Exper Clin Psychopharmacol 9:74–82CrossRefGoogle Scholar
  40. Le AD, Li Z, Funk D, Shram M, Li TK, Shaham Y (2006) Increased vulnerability to nicotine self-administration and relapse in alcohol-naive offspring of rats selectively bred for high alcohol intake. J Neurosci 26:1872–1879PubMedCrossRefGoogle Scholar
  41. Logan GD, Schachar RJ, Tannock RT (1997) Impulsivity and inhibitory control. Psychol Sci 8:60–64CrossRefGoogle Scholar
  42. Mackintosh NJ (1974) The psychology of animal learning. Academic, New YorkGoogle Scholar
  43. Marks MJ, Campbell SM, Romm E, Collins AC (1991) Genotype influences the development of tolerance to nicotine in the mouse. J Pharmacol Exper Ther 259:392–402Google Scholar
  44. Masse LC, Tremblay RE (1997) Behavior of boys in kindergarten and the onset of substance use during adolescence. Arch Gen Psychiatr 54:62–68PubMedGoogle Scholar
  45. McClernon FJ, Kollins SH, Lutz AM, Fitzgerald DP, Murray DW, Redman C, Rose JE (2008) Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study. Psychopharmacology 197:95–105PubMedCrossRefGoogle Scholar
  46. McNair DM, Loor M, Droppelman LF (1971) Profile of Mood States. Educational and Testing Service, San DiegoGoogle Scholar
  47. Milberger S, Biederman J, Faraone SV, Chen L, Jones J (1997) ADHD is associated with early initiation of cigarette smoking in children and adolescents. J Amer Acad Child Adol Psychiatr 36:37–44CrossRefGoogle Scholar
  48. Mitchell SH (1999) Measures of impulsivity in cigarette smokers and non-smokers. Psychopharmacology 146:455–464PubMedCrossRefGoogle Scholar
  49. Murphy P, Schachar R (2000) Use of self-ratings in the assessment of symptoms of attention deficit hyperactivity disorder in adults. Amer J Psychiatr 157:1156–1159CrossRefGoogle Scholar
  50. O’Connor RJ, Kozlowski LT, Vandenbergh DJ, Strasser AA, Grant MD, Vogler GP (2005) An examination of early smoking experiences and smoking status in a national cross-sectional sample. Addiction 100:1352–1357PubMedCrossRefGoogle Scholar
  51. Ohmura Y, Takahashi T, Kitamura N (2005) Discounting delayed and probabilistic monetary gains and losses by smokers of cigarettes. Psychopharmacology 182:508–515PubMedCrossRefGoogle Scholar
  52. Pattij T, Vandenschuren LJMJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29:192–199PubMedCrossRefGoogle Scholar
  53. Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt Impulsiveness Scale. J Clin Psychol 51:768–774PubMedCrossRefGoogle Scholar
  54. Perkins KA (1999) Baseline-dependency of nicotine effects: a review. Behav Pharmacol 10:597–615PubMedGoogle Scholar
  55. Perkins KA (2004) Commentary: obstacles to determining individual differences in the efficacy of smoking cessation medications. Nic Tobacco Res 6:765–767CrossRefGoogle Scholar
  56. Perkins KA (2008) Sex differences in nicotine reinforcement and reward: influences on the persistence of tobacco smoking. In: Bevins R, Caggiula AR (eds) The motivational impact of nicotine and its role in tobacco use. Springer, New YorkGoogle Scholar
  57. Perkins KA, Epstein LH, Stiller R, Jennings JR, Christiansen C, McCarthy T (1986) An aerosol spray alternative to cigarette smoking in the study of the behavioral and physiological effects of nicotine. Behav Res Meth Instr Comput 18:420–426Google Scholar
  58. Perkins KA, Grobe JE, Fonte C, Goettler J, Caggiula AR, Reynolds WA, Stiller RL, Scierka A, Jacob RG (1994a) Chronic and acute tolerance to subjective, behavioral, and cardiovascular effects of nicotine in humans. J Pharmacol Exper Ther 270:628–638Google Scholar
  59. Perkins KA, Sexton JE, Reynolds WA, Grobe JE, Fonte C, Stiller RL (1994b) Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking vs. nasal spray. Pharmacol Biochem Behav 47:295–299PubMedCrossRefGoogle Scholar
  60. Perkins KA, Grobe JE, Weiss D, Fonte C, Caggiula A (1996) Nicotine preference in smokers as a function of smoking abstinence. Pharmacol Biochem Behav 55:257–263PubMedCrossRefGoogle Scholar
  61. Perkins KA, Donny E, Caggiula AR (1999) Sex differences in nicotine effects and self-administration: review of human and animal evidence. Nic Tobacco Res 1:301–315CrossRefGoogle Scholar
  62. Perkins KA, Gerlach D, Broge M, Grobe JE, Wilson A (2000) Greater sensitivity to subjective effects of nicotine in nonsmokers high in sensation seeking. Exper Clin Psychopharmacol 8:462–471CrossRefGoogle Scholar
  63. Perkins KA, Gerlach D, Broge M, Grobe JE, Sanders M, Fonte C, Vender J, Cherry C, Wilson A (2001a) Dissociation of nicotine tolerance from tobacco dependence in humans. J Pharmacol Exper Ther 296:849–856Google Scholar
  64. Perkins KA, Gerlach D, Broge M, Fonte C, Wilson A (2001b) Reinforcing effects of nicotine as a function of smoking status. Exper Clin Psychopharmacol 9:243–250CrossRefGoogle Scholar
  65. Perkins KA, Broge M, Gerlach D, Sanders M, Grobe JE, Cherry C, Wilson AS (2002a) Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking. Health Psychol 21:332–339PubMedCrossRefGoogle Scholar
  66. Perkins KA, Jacobs L, Sanders M, Caggiula AR (2002b) Sex differences in the subjective and reinforcing effects of cigarette nicotine dose. Psychopharmacology 163:194–201PubMedCrossRefGoogle Scholar
  67. Perkins KA, Jetton C, Stolinski A, Fonte C, Conklin CA (2003) The consistency of acute responses to nicotine in humans. Nic Tobacco Res 5:877–884CrossRefGoogle Scholar
  68. Pomerleau OF (1995) Individual differences in sensitivity to nicotine: implications for genetic research on nicotine dependence. Behav Genet 25:161–177PubMedCrossRefGoogle Scholar
  69. Pomerleau OF, Pomerleau CS, Rose JE (1989) Controlled dosing of nicotine: a review of problems and progress. Ann Behav Med 11:158–163CrossRefGoogle Scholar
  70. Pomerleau OF, Pomerleau CS, Namenek RJ (1998) Early experiences with tobacco among women smokers, ex-smokers, and never-smokers. Addiction 93:595–599PubMedCrossRefGoogle Scholar
  71. Pomerleau CS, Downey KK, Snedecor SM, Mehringer AM, Marks JL, Pomerleau OF (2003) Smoking patterns and abstinence effects in smokers with no ADHD, childhood ADHD, and adult ADHD symptomatology. Addict Behav 28:1149–1157PubMedCrossRefGoogle Scholar
  72. Pomerleau CS, Pomerleau OF, Snedecor SM, Gaulrapp S, Kardia SL (2004) Heterogeneity in phenotypes based on smoking status in the Great Lakes Smoker Sibling Registry. Addict Behav 29:1851–1855PubMedCrossRefGoogle Scholar
  73. Popke EJ, Mayorga AJ, Fogle CM, Paule MG (2000) Effects of acute nicotine on several operant behaviors in rats. Pharmacol Biochem Behav 65:247–254PubMedCrossRefGoogle Scholar
  74. Potter AS, Newhouse PA (2004) Effects of acute nicotine administration on behavioral inhibition in adolescents with attention-deficit/hyperactivity disorder. Psychopharmacology 176:182–194PubMedCrossRefGoogle Scholar
  75. Potter AS, Newhouse PA (2008) Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav 88:407–417PubMedCrossRefGoogle Scholar
  76. Ray R, Jepson C, Patterson F, Strasser AA, Rukstalis M, Perkins K, Lynch K, O’Malley S, Berrettini W, Lerman C (2006) Association of OPRM1 Asn40Asp variant with the relative reinforcing value of nicotine in female smokers. Psychopharmacology 188:355–363PubMedCrossRefGoogle Scholar
  77. Reynolds B, Patak M, Shroff P, Penfold RB, Melanko S, Duhig AM (2007) Laboratory and self-report assessments of impulsive behavior in adolescent daily smokers and nonsmokers. Exper Clin Psychopharmacol 15:264–271CrossRefGoogle Scholar
  78. Schechter MD, Meehan SM, Schechter JB (1995) Genetic selection for nicotine activity in mice correlates with conditioned place preference. Eur J Pharmacol 279:59–64PubMedCrossRefGoogle Scholar
  79. Schneider W, Shiffrin R (1977) Controlled and automatic human information processing: I. Detection, search, and attention. Psychol Rev 84:1–66CrossRefGoogle Scholar
  80. Schneider NG, Lunell E, Olmstead RE, Fagerstrom K-O (1996) Clinical pharmacokinetics of nasal nicotine delivery—a review and comparison to other nicotine systems. Clin Pharmacokin 31:65–80CrossRefGoogle Scholar
  81. Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Personal Soc Psychol 54:1063–1070CrossRefGoogle Scholar
  82. Yoon JH, Higgins ST (2008) Turning k on its head: comments on use of an ED50 in delay discounting research. Drug Alc Depend 95:169–172CrossRefGoogle Scholar
  83. Zuckerman M (1994) Behavioral expressions and biosocial bases of sensation seeking. Cambridge Univ Press, Cambridge, UKGoogle Scholar
  84. Zuckerman M, Kuhlman DM, Thornquist M, Kiers H (1991) Five (or three) robust questionnaire scale factors of personality without culture. Pers Individ Differ 12(9):929–941CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Kenneth A. Perkins
    • 1
  • Caryn Lerman
    • 2
  • Sarah B. Coddington
    • 1
  • Christopher Jetton
    • 3
  • Joshua L. Karelitz
    • 1
  • John A. Scott
    • 1
  • Annette S. Wilson
    • 4
  1. 1.Western Psychiatric Institute & ClinicUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PsychologyUniversity of California at Los AngelesLos AngelesUSA
  4. 4.Department of Environmental and Occupational Health, Salk HallUniversity of PittsburghPittsburghUSA

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