Psychopharmacology

, Volume 222, Issue 4, pp 701–708

μ-Opioid receptor availability in the amygdala is associated with smoking for negative affect relief

  • Mary Falcone
  • Allison B. Gold
  • E. Paul Wileyto
  • Riju Ray
  • Kosha Ruparel
  • Andrew Newberg
  • Jacob Dubroff
  • Jean Logan
  • Jon-Kar Zubieta
  • Julie A. Blendy
  • Caryn Lerman
Original Investigation

Abstract

Rationale

The perception that smoking relieves negative affect contributes to smoking persistence. Endogenous opioid neurotransmission, and the μ-opioid receptor (MOR) in particular, plays a role in affective regulation and is modulated by nicotine.

Objectives

We examined the relationship of MOR binding availability in the amygdala to the motivation to smoke for negative affect relief and to the acute effects of smoking on affective responses.

Methods

Twenty-two smokers were scanned on two separate occasions after overnight abstinence using [11C]carfentanil positron emission tomography imaging: after smoking a nicotine-containing cigarette and after smoking a denicotinized cigarette. Self-reports of smoking motives were collected at baseline, and measures of positive and negative affect were collected pre- and post- cigarette smoking.

Results

Higher MOR availability in the amygdala was associated with motivation to smoke to relieve negative affect. However, MOR availability was unrelated to changes in affect after smoking either cigarette.

Conclusions

Increased MOR availability in amygdala may underlie the motivation to smoke for negative affective relief. These results are consistent with previous data highlighting the role of MOR neurotransmission in smoking behavior.

Keywords

Smoking motivation μ-Opioid receptor Amygdala Affect regulation 

References

  1. Balerio GN, Aso E, Maldonado R (2005) Involvement of the opioid system in the effects induced by nicotine on anxiety-like behaviour in mice. Psychopharmacology (Berl) 181:260–269CrossRefGoogle Scholar
  2. Benowitz NL, Jacob P 3rd, Herrera B (2006) Nicotine intake and dose response when smoking reduced-nicotine content cigarettes. Clin Pharmacol Ther 80:703–714PubMedCrossRefGoogle Scholar
  3. Berrendero F, Kieffer BL, Maldonado R (2002) Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice. J Neurosci 22:10935–10940PubMedGoogle Scholar
  4. Boyadjieva NI, Sarkar DK (1997) The secretory response of hypothalamic beta-endorphin neurons to acute and chronic nicotine treatments and following nicotine withdrawal. Life Sci 61:PL59–PL66PubMedCrossRefGoogle Scholar
  5. 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 12:305–316PubMedCrossRefGoogle Scholar
  6. CDC (2009) Center for Disease Control: Cigarette smoking among adults and trends in smoking cessation - United States, 2008. MMWR Morb Mortal Wkly Rep 58:1227–1232Google Scholar
  7. Colvin PJ, Mermelstein RJ (2010) Adolescents' smoking outcome expectancies and acute emotional responses following smoking. Nicotine Tob Res 12:1203–1210PubMedCrossRefGoogle Scholar
  8. Conklin CA, Perkins KA (2005) Subjective and reinforcing effects of smoking during negative mood induction. J Abnorm Psychol 114:153–164PubMedCrossRefGoogle Scholar
  9. Costa PT Jr, McCrae RR, Bosse R (1980) Smoking motive factors: a review and replication. Int J Addict 15:537–549PubMedGoogle Scholar
  10. Davidson RJ, Irwin W (1999) The functional neuroanatomy of emotion and affective style. Trends Cogn Sci 3:11–21PubMedCrossRefGoogle Scholar
  11. Diekhof EK, Geier K, Falkai P, Gruber O (2011) Fear is only as deep as the mind allows a coordinate-based meta-analysis of neuroimaging studies on the regulation of negative affect. NeuroImage 58:275–285PubMedCrossRefGoogle Scholar
  12. Diener E, Emmons RA (1984) The independence of positive and negative affect. J Pers Soc Psychol 47:1105–1117PubMedCrossRefGoogle Scholar
  13. Epperson CN, Toll B, Wu R, Amin Z, Czarkowski KA, Jatlow P, Mazure CM, O'Malley SS (2010) Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch. Drug Alcohol Depend 112:1–8PubMedCrossRefGoogle Scholar
  14. Greenwald M, Johanson CE, Bueller J, Chang Y, Moody DE, Kilbourn M, Koeppe R, Zubieta JK (2007) Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices. Biol Psychiatry 61:101–110PubMedCrossRefGoogle Scholar
  15. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127PubMedCrossRefGoogle Scholar
  16. Hirvonen J, Aalto S, Hagelberg N, Maksimow A, Ingman K, Oikonen V, Virkkala J, Nagren K, Scheinin H (2009) Measurement of central mu-opioid receptor binding in vivo with PET and [11C]carfentanil: a test–retest study in healthy subjects. Eur J Nucl Med Mol Imaging 36:275–286PubMedCrossRefGoogle Scholar
  17. Horn D, Waingrow S (1966) Some dimensions of a model for smoking behavior change. Am J Public Health Nations Health 56(Suppl 56):21–26PubMedCrossRefGoogle Scholar
  18. Houdi AA, Pierzchala K, Marson L, Palkovits M, Van Loon GR (1991) Nicotine-induced alteration in Tyr–Gly–Gly and Met-enkephalin in discrete brain nuclei reflects altered enkephalin neuron activity. Peptides 12:161–166PubMedCrossRefGoogle Scholar
  19. Hutchison KE, Monti PM, Rohsenow DJ, Swift RM, Colby SM, Gnys M, Niaura RS, Sirota AD (1999) Effects of naltrexone with nicotine replacement on smoking cue reactivity: preliminary results. Psychopharmacology (Berl) 142:139–143CrossRefGoogle Scholar
  20. Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, Suhara T, Suzuki K, Innis RB, Carson RE (2003) Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J Cereb Blood Flow Metab 23:1096–1112PubMedCrossRefGoogle Scholar
  21. Juliano LM, Fucito LM, Harrell PT (2011) The influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking. Exp Clin Psychopharmacol 19:105–115PubMedCrossRefGoogle Scholar
  22. Karp JS, Surti S, Daube-Witherspoon ME, Freifelder R, Cardi CA, Adam LE, Bilger K, Muehllehner G (2003) Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors. J Nucl Med 44:1340–1349PubMedGoogle Scholar
  23. Kassel JD, Evatt DP, Greenstein JE, Wardle MC, Yates MC, Veilleux JC (2007) The acute effects of nicotine on positive and negative affect in adolescent smokers. J Abnorm Psychol 116:543–553PubMedCrossRefGoogle Scholar
  24. Kim MJ, Loucks RA, Palmer AL, Brown AC, Solomon KM, Marchante AN, Whalen PJ (2011) The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety. Behav Brain Res 223:403–410PubMedCrossRefGoogle Scholar
  25. Lee MR, Gallen CL, Zhang X, Hodgkinson CA, Goldman D, Stein EA, Barr CS (2011) Functional Polymorphism of the Mu-Opioid Receptor Gene (OPRM1) Influences Reinforcement Learning in Humans. PLoS One 6:e24203PubMedCrossRefGoogle Scholar
  26. Lerman C, Audrain-McGovern J (2010) Reinforcing effects of smoking: more than a feeling. Biol Psychiatry 67:699–701PubMedCrossRefGoogle Scholar
  27. Lerman C, Audrain J, Orleans CT, Boyd R, Gold K, Main D, Caporaso N (1996) Investigation of mechanisms linking depressed mood to nicotine dependence. Addict Behav 21:9–19PubMedCrossRefGoogle Scholar
  28. Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG (1998) Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Health Psychol 17:56–62PubMedCrossRefGoogle Scholar
  29. Lerman C, Roth D, Kaufmann V, Audrain J, Hawk L, Liu A, Niaura R, Epstein L (2002) Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Drug Alcohol Depend 67:219–223PubMedCrossRefGoogle Scholar
  30. Lerman C, Wileyto EP, Patterson F, Rukstalis M, Audrain-McGovern J, Restine S, Shields PG, Kaufmann V, Redden D, Benowitz N, Berrettini WH (2004) The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J 4:184–192PubMedCrossRefGoogle Scholar
  31. Mague SD, Blendy JA (2010) OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models. Drug Alcohol Depend 108:172–182PubMedCrossRefGoogle Scholar
  32. Mahler SV, Berridge KC (2009) Which cue to "want?" Central amygdala opioid activation enhances and focuses incentive salience on a prepotent reward cue. J Neurosci 29:6500–6513PubMedCrossRefGoogle Scholar
  33. Marty MA, Erwin VG, Cornell K, Zgombick JM (1985) Effects of nicotine on beta-endorphin, alpha MSH, and ACTH secretion by isolated perfused mouse brains and pituitary glands, in vitro. Pharmacol Biochem Behav 22:317–325PubMedCrossRefGoogle Scholar
  34. Mills RH, Sohn RK, Micevych PE (2004) Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats. J Neurosci 24:947–955PubMedCrossRefGoogle Scholar
  35. Munafo MR, Elliot KM, Murphy MF, Walton RT, Johnstone EC (2007) Association of the mu-opioid receptor gene with smoking cessation. Pharmacogenomics J 7:353–361PubMedCrossRefGoogle Scholar
  36. O'Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee SA, Cooney NL, Blakeslee A, Meandzija B, Romano-Dahlgard D, Wu R, Makuch R, Jatlow P (2006) A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med 166:667–674PubMedCrossRefGoogle Scholar
  37. Perkins KA, Giedgowd GE, Karelitz JL, Conklin CA, Parzynski CS (2011) Expectancy for negative affect relief due to smoking may not be predictive under acute mood situations. Exp Clin PsychopharmacolGoogle Scholar
  38. Perkins KA, Karelitz JL, Giedgowd GE, Conklin CA, Sayette MA (2010) Differences in negative mood-induced smoking reinforcement due to distress tolerance, anxiety sensitivity, and depression history. Psychopharmacology (Berl) 210:25–34CrossRefGoogle Scholar
  39. Perkins KA, Lerman C, Grottenthaler A, Ciccocioppo MM, Milanak M, Conklin CA, Bergen AW, Benowitz NL (2008) Dopamine and opioid gene variants are associated with increased smoking reward and reinforcement owing to negative mood. Behav Pharmacol 19:641–649PubMedCrossRefGoogle Scholar
  40. Pessoa L (2010) Emergent processes in cognitive-emotional interactions. Dialogues Clin Neurosci 12:433–448PubMedGoogle Scholar
  41. Pfeiffer A, Pasi A, Mehraein P, Herz A (1982) Opiate receptor binding sites in human brain. Brain Res 248:87–96PubMedCrossRefGoogle Scholar
  42. Ray R, Jepson C, Patterson F, Strasser A, Rukstalis M, Perkins K, Lynch KG, O'Malley S, Berrettini WH, Lerman C (2006) Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology (Berl) 188:355–363CrossRefGoogle Scholar
  43. Ray R, Jepson C, Wileyto EP, Dahl JP, Patterson F, Rukstalis M, Pinto A, Berrettini W, Lerman C (2007) Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial. Nicotine Tob Res 9:1237–1241PubMedCrossRefGoogle Scholar
  44. Ray R, Ruparel K, Newberg A, Wileyto EP, Loughead JW, Divgi C, Blendy JA, Logan J, Zubieta JK, Lerman C (2011) Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proc Natl Acad Sci U S A 108:9268–9273PubMedCrossRefGoogle Scholar
  45. Ribeiro SC, Kennedy SE, Smith YR, Stohler CS, Zubieta JK (2005) Interface of physical and emotional stress regulation through the endogenous opioid system and mu-opioid receptors. Prog Neuropsychopharmacol Biol Psychiatry 29:1264–1280PubMedCrossRefGoogle Scholar
  46. Rose JE (2006) Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology (Berl) 184:274–285CrossRefGoogle Scholar
  47. Scott DJ, Domino EF, Heitzeg MM, Koeppe RA, Ni L, Guthrie S, Zubieta JK (2007) Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans. Neuropsychopharmacology 32:450–457PubMedCrossRefGoogle Scholar
  48. Shiffman S (1993) Assessing smoking patterns and motives. J Consult Clin Psychol 61:732–742PubMedCrossRefGoogle Scholar
  49. Shiffman S, Hufford M, Hickcox M, Paty JA, Gnys M, Kassel JD (1997) Remember that? A comparison of real-time versus retrospective recall of smoking lapses. J Consult Clin Psychol 65:292–300PubMedCrossRefGoogle Scholar
  50. Shiffman S, Prange M (1988) Self-reported and self-monitored smoking patterns. Addict Behav 13:201–204PubMedCrossRefGoogle Scholar
  51. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23(Suppl 1):S208–S219PubMedCrossRefGoogle Scholar
  52. Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK (2006) Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci 26:5777–5785PubMedCrossRefGoogle Scholar
  53. Strasser AA, Ashare RL, Kozlowski LT, Pickworth WB (2005a) The effect of filter vent blocking and smoking topography on carbon monoxide levels in smokers. Pharmacol Biochem Behav 82:320–329PubMedCrossRefGoogle Scholar
  54. Strasser AA, Kaufmann V, Jepson C, Perkins KA, Pickworth WB, Wileyto EP, Rukstalis M, Audrain-McGovern J, Lerman C (2005b) Effects of different nicotine replacement therapies on postcessation psychological responses. Addict Behav 30:9–17PubMedCrossRefGoogle Scholar
  55. Strasser AA, Lerman C, Sanborn PM, Pickworth WB, Feldman EA (2007) New lower nicotine cigarettes can produce compensatory smoking and increased carbon monoxide exposure. Drug Alcohol Depend 86:294–300PubMedCrossRefGoogle Scholar
  56. Tate JC, Stanton AL (1990) Assessment of the validity of the Reasons for Smoking scale. Addict Behav 15:129–135PubMedCrossRefGoogle Scholar
  57. Walsh Z, Epstein A, Munisamy G, King A (2008) The impact of depressive symptoms on the efficacy of naltrexone in smoking cessation. J Addict Dis 27:65–72PubMedCrossRefGoogle Scholar
  58. Walters CL, Cleck JN, Kuo YC, Blendy JA (2005) Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron 46:933–943PubMedCrossRefGoogle Scholar
  59. Wewers ME, Dhatt RK, Snively TA, Tejwani GA (1999) The effect of chronic administration of nicotine on antinociception, opioid receptor binding and met-enkelphalin levels in rats. Brain Res 822:107–113PubMedCrossRefGoogle Scholar
  60. WHO (2009) World Health Organization. WHO Report on the global tobacco epidemic.Google Scholar
  61. Zhang L, Kendler KS, Chen X (2006) The mu-opioid receptor gene and smoking initiation and nicotine dependence. Behav Brain Funct 2:28PubMedCrossRefGoogle Scholar
  62. Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS (2005) Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 25:7754–7762PubMedCrossRefGoogle Scholar
  63. Zubieta JK, Dannals RF, Frost JJ (1999) Gender and age influences on human brain mu-opioid receptor binding measured by PET. Am J Psychiatry 156:842–848PubMedGoogle Scholar
  64. Zubieta JK, Ketter TA, Bueller JA, Xu Y, Kilbourn MR, Young EA, Koeppe RA (2003) Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Arch Gen Psychiatry 60:1145–1153PubMedCrossRefGoogle Scholar
  65. Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS (2001) Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 293:311–315PubMedCrossRefGoogle Scholar
  66. Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS (2002) mu-opioid receptor-mediated antinociceptive responses differ in men and women. J Neurosci 22:5100–5107PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Mary Falcone
    • 1
    • 2
  • Allison B. Gold
    • 2
  • E. Paul Wileyto
    • 2
  • Riju Ray
    • 2
  • Kosha Ruparel
    • 3
  • Andrew Newberg
    • 4
  • Jacob Dubroff
    • 5
  • Jean Logan
    • 6
  • Jon-Kar Zubieta
    • 7
  • Julie A. Blendy
    • 1
  • Caryn Lerman
    • 2
  1. 1.Department of PharmacologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Center for Interdisciplinary Research on Nicotine Addiction, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Brain Behavior Laboratory, Neuropsychiatry DepartmentHospital of the University of PennsylvaniaPhiladelphiaUSA
  4. 4.Myrna Brind Center of Integrative Medicine, Department of Emergency Medicine and RadiologyThomas Jefferson UniversityPhiladelphiaUSA
  5. 5.Department of Nuclear MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  6. 6.Medical DepartmentBrookhaven National LaboratoryUptonUSA
  7. 7.Molecular and Behavioral Neuroscience InstituteUniversity of MichiganAnn ArborUSA

Personalised recommendations