https://www.nature.com/articles/s41386-020-0611-5

Comment; In the Nucleus accumbens, nicotine has a stronger effect on anticipation than on outcome.

Neuropsychopharmacology (2020)Cite this article

Abstract

Nicotine enhances the reinforcement of non-drug rewards by increasing nucleus accumbens (NAcc) reactivity to anticipatory cues. This anticipatory effect is selective as no clear evidence has emerged showing that nicotine acutely changes reward receipt reactivity. However, repeated rewarding experiences shift peak brain reactivity from hedonic reward outcome to the motivational anticipatory cue yielding more habitual cue-induced behavior. Given nicotine’s influence on NAcc reactivity and connectivity, it is plausible that nicotine acutely induces this shift and alters NAcc functional connectivity during reward processing. To evaluate this currently untested hypothesis, a randomized crossover design was used in which healthy non-smokers were administered placebo and nicotine (2-mg lozenge). Brain activation to monetary reward anticipation and outcome was evaluated with functional magnetic resonance imaging. Relative to placebo, nicotine induced more NAcc reactivity to reward anticipation. Greater NAcc activation during anticipation was significantly associated with lower NAcc activation to outcome. During outcome, nicotine reduced NAcc functional connectivity with cortical regions including the anterior cingulate cortex, orbitofrontal cortex, and insula. These regions showed the same negative relationship between reward anticipation and outcome as noted in the NAcc. The current findings significantly improve our understanding of how nicotine changes corticostriatal circuit function and communication during distinct phases of reward processing and critically show that these alterations happen acutely following a single dose. The implications of this work explain nicotinic modulation of general reward function, which offer insights into the initial drive to smoke and the subsequent difficulty in cessation.

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References

  1. 1.Stolerman IP, Jarvis M. The scientific case that nicotine is addictive. Psychopharmacology. 1995;117:2–10.
  2. 2.Pontieri FE, Tanda G, Orzi F, Di Chiara G. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature. 1996;382:255.
  3. 3.Rice ME, Cragg SJ. Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci. 2004;7:583.
  4. 4.Wang KS, Smith DV, Delgado MR. Using fMRI to study reward processing in humans: past, present, and future. J Neurophysiol. 2016;115:1664–78.
  5. 5.Delgado MR. Reward‐related responses in the human striatum. Ann N Y Acad Sci. 2007;1104:70–88.
  6. 6.Zhang T, Zhang L, Liang Y, Siapas AG, Zhou F-M, Dani JA. Dopamine signaling differences in the nucleus accumbens and dorsal striatum exploited by nicotine. J Neurosci. 2009;29:4035–43.
  7. 7.Barr RS, Pizzagalli DA, Culhane MA, Goff DC, Evins AE. A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence. Biol Psychiatry. 2008;63:1061–5.
  8. 8.Olausson P, Jentsch JD, Taylor JR. Nicotine enhances responding with conditioned reinforcement. Psychopharmacology. 2004;171:173–8.
  9. 9.Collins AL, Aitken TJ, Greenfield VY, Ostlund SB, Wassum KM. Nucleus accumbens acetylcholine receptors modulate dopamine and motivation. Neuropsychopharmacology. 2016;41:2830.
  10. 10.Sun N, Laviolette SR, Group AR. Dopamine receptor blockade modulates the rewarding and aversive properties of nicotine via dissociable neuronal activity patterns in the nucleus accumbens. Neuropsychopharmacology. 2014;39:2799.
  11. 11.Jerlhag E, Engel JA. Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice. Drug Alcohol Depend. 2011;117:126–31.
  12. 12.Spina L, Fenu S, Longoni R, Rivas E, Di Chiara G. Nicotine-conditioned single-trial place preference: selective role of nucleus accumbens shell dopamine D 1 receptors in acquisition. Psychopharmacology. 2006;184:447–55.
  13. 13.Walters CL, Cleck JN, Kuo Y-c, Blendy JA. μ-Opioid receptor and CREB activation are required for nicotine reward. Neuron. 2005;46:933–43.
  14. 14.Olney JJ, Warlow SM, Naffziger EE, Berridge KC. Current perspectives on incentive salience and applications to clinical disorders. Curr Opin Behav Sci. 2018;22:59–69.
  15. 15.Ostlund SB, LeBlanc KH, Kosheleff AR, Wassum KM, Maidment NT. Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure. Neuropsychopharmacology. 2014;39:2441.
  16. 16.Peciña S, Berridge KC. Dopamine or opioid stimulation of nucleus accumbens similarly amplify cue‐triggered ‘wanting’for reward: entire core and medial shell mapped as substrates for PIT enhancement. Eur J Neurosci. 2013;37:1529–40.
  17. 17.Hickey C, Peelen MV. Neural mechanisms of incentive salience in naturalistic human vision. Neuron. 2015;85:512–8.
  18. 18.Berridge KC, Robinson TE. Liking, wanting, and the incentive-sensitization theory of addiction. Am Psychologist. 2016;71:670.
  19. 19.Smith KS, Mahler SV, Peciña S, Berridge KC. Hedonic hotspots: generating sensory pleasure in the brain. In: Kringelbach ML, Berridge KC (eds). Pleasures of the brain. New York, NY: Oxford University Press; 2010. p. 27–49.
  20. 20.Smith KS, Berridge KC. The ventral pallidum and hedonic reward: neurochemical maps of sucrose “liking” and food intake. J Neurosci. 2005;25:8637–49.
  21. 21.Mahler SV, Smith KS, Berridge KC. Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’of a sweet reward. Neuropsychopharmacology. 2007;32:2267.
  22. 22.Castro DC, Berridge KC. Opioid hedonic hotspot in nucleus accumbens shell: mu, delta, and kappa maps for enhancement of sweetness “liking” and “wanting”. J Neurosci. 2014;34:4239–50.
  23. 23.Oldham S, Murawski C, Fornito A, Youssef G, Yücel M, Lorenzetti V. The anticipation and outcome phases of reward and loss processing: a neuroimaging meta‐analysis of the monetary incentive delay task. Hum Brain Mapp. 2018;39:3398–418.
  24. 24.Rose EJ, Ross TJ, Salmeron BJ, Lee M, Shakleya DM, Huestis MA, et al. Acute nicotine differentially impacts anticipatory valence-and magnitude-related striatal activity. Biol. Psychiatry. 2013;73:280–8.
  25. 25.Moran LV, Stoeckel LE, Wang K, Caine CE, Villafuerte R, Calderon V, et al. Nicotine increases activation to anticipatory valence cues in anterior insula and striatum. Nicotine Tob Res. 2017;20:851–8.
  26. 26.Bühler M, Vollstädt-Klein S, Kobiella A, Budde H, Reed LJ, Braus DF, et al. Nicotine dependence is characterized by disordered reward processing in a network driving motivation. Biol Psychiatry. 2010;67:745–52.
  27. 27.Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev. 1998;28:309–69.
  28. 28.Berridge KC. The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology. 2007;191:391–431.
  29. 29.Berridge KC. From prediction error to incentive salience: mesolimbic computation of reward motivation. Eur J Neurosci. 2012;35:1124–43.
  30. 30.Zhang L, Dong Y, Doyon WM, Dani JA. Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in the nucleus accumbens. Biol Psychiatry. 2012;71:184–91.
  31. 31.Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, et al. Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav. 2001;70:515–30.
  32. 32.Howe WM, Berry AS, Francois J, Gilmour G, Carp JM, Tricklebank M, et al. Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans. J Neurosci. 2013;33:8742–52.
  33. 33.Brunzell DH, Mineur YS, Neve RL, Picciotto MR. Nucleus accumbens CREB activity is necessary for nicotine conditioned place preference. Neuropsychopharmacology. 2009;34:1993.
  34. 34.Madayag A, Lobner D, Kau KS, Mantsch JR, Abdulhameed O, Hearing M, et al. Repeated N-acetylcysteine administration alters plasticity-dependent effects of cocaine. J Neurosci. 2007;27:13968–76.
  35. 35.Picciotto MR, Zoli M, Rimondini R, Léna C, Marubio LM, Pich EM, et al. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391:173.
  36. 36.Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10:561.
  37. 37.Pistillo F, Clementi F, Zoli M, Gotti C. Nicotinic, glutamatergic and dopaminergic synaptic transmission and plasticity in the mesocorticolimbic system: focus on nicotine effects. Prog Neurobiol. 2015;124:1–27.
  38. 38.Picciotto MR, Mineur YS. Molecules and circuits involved in nicotine addiction: the many faces of smoking. Neuropharmacology. 2014;76:545–53.
  39. 39.Admon R, Kaiser R, Dillon D, Beltzer M, Goer F, Olson D, et al. Dopaminergic enhancement of striatal response to reward in major depression. Am J psychiatry. 2017;174:378.
  40. 40.Knutson B, Fong GW, Adams CM, Varner JL, Hommer D. Dissociation of reward anticipation and outcome with event-related fMRI. Neuroreport. 2001;12:3683–87.
  41. 41.Janes AC, Zegel M, Ohashi K, Betts J, Molokotos E, Olson D, et al. Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder. Neuropsychopharmacology. 2018;43:2445.
  42. 42.First MB, Spitzer RL, Gibbon M, Williams JB. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. SCID-I/P. New York: Biometrics Research, New York State Psychiatric Institute; 2002.
  43. 43.Choi JH, Dresler CM, Norton MR, Strahs KR. Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res. 2003;5:635–44.
  44. 44.Benowitz NL, III PJ. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Therapeutics. 1984;35:499–504.
  45. 45.Benowitz N. Systemic absorption and effects of nicotine from smokeless tobacco. Adv Dent Res. 1997;11:336–41.
  46. 46.Benowitz NL, Porchet H, Sheiner L, Jacob IIIP. Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Therapeutics. 1988;44:23–8.
  47. 47.Ziegler UE, Kauczok J, Dietz UA, Reith HB, Schmidt K. Clinical correlation between the consumption of nicotine and cotinine concentrations in urine and serum by competitive enzyme-linked immunosorbent assay. Pharmacology. 2004;72:254–9.
  48. 48.Woolrich MW, Behrens TE, Beckmann CF, Jenkinson M, Smith SM. Multilevel linear modelling for FMRI group analysis using Bayesian inference. NeuroImage. 2004;21:1732–47.
  49. 49.Woo C-W, Krishnan A, Wager TD. Cluster-extent based thresholding in fMRI analyses: pitfalls and recommendations. NeuroImage. 2014;91:412–9.
  50. 50.Worsley K, Jezzard P, Matthews P, Smith S. Functional MRI: an introduction to methods. In: Jezzard P, Matthews PM, Smith SM. (eds). New York, NY: Oxford University Press. 2001. p. 251–70.
  51. 51.Pecina S, Berridge KC. Hedonic hot spot in nucleus accumbens shell: where do μ-opioids cause increased hedonic impact of sweetness? J Neurosci. 2005;25:11777–86.
  52. 52.Smith KS, Berridge KC. Opioid limbic circuit for reward: interaction between hedonic hotspots of nucleus accumbens and ventral pallidum. J Neurosci. 2007;27:1594–605.
  53. 53.Chaudhri N, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, et al. Operant responding for conditioned and unconditioned reinforcers in rats is differentially enhanced by the primary reinforcing and reinforcement-enhancing effects of nicotine. Psychopharmacology. 2006;189:27–36.
  54. 54.Palmatier MI, Liu X, Matteson GL, Donny EC, Caggiula AR, Sved AF. Conditioned reinforcement in rats established with self-administered nicotine and enhanced by noncontingent nicotine. Psychopharmacology. 2007;195:235–43.
  55. 55.Overby PF, Daniels CW, Del Franco A, Goenaga J, Powell GL, Gipson CD, et al. Effects of nicotine self-administration on incentive salience in male Sprague Dawley rats. Psychopharmacology. 2018;235:1121–30.
  56. 56.Versaggi CL, King CP, Meyer PJ. The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol. Psychopharmacology. 2016;233:2985–97.
  57. 57.Schultz W. Getting formal with dopamine and reward. Neuron. 2002;36:241–63.
  58. 58.Schultz W. Neuronal reward and decision signals: from theories to data. Physiol Rev. 2015;95:853–951.
  59. 59.Schultz W. Updating dopamine reward signals. Curr Opin Neurobiol. 2013;23:229–38.
  60. 60.Reid MS, Mickalian JD, Delucchi KL, Hall SM, Berger SP. An acute dose of nicotine enhances cue-induced cocaine craving. Drug Alcohol Depend. 1998;49:95–104.
  61. 61.Horger BA, Giles MK, Schenk S. Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine. Psychopharmacology. 1992;107:271–6.
  62. 62.Hogarth L, Chase HW. Parallel goal-directed and habitual control of human drug-seeking: Implications for dependence vulnerability. J Exp Psychol: Anim Behav Process. 2011;37:261.
  63. 63.Hogarth L, Balleine BW, Corbit LH, Killcross S. Associative learning mechanisms underpinning the transition from recreational drug use to addiction. Ann N Y Acad Sci. 2013;1282:12–24.
  64. 64.Hu Y, Salmeron BJ, Gu H, Stein EA, Yang Y. Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction. JAMA Psychiatry. 2015;72:584–92.
  65. 65.Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35:4–26.
  66. 66.Padoa-Schioppa C, Assad JA. Neurons in the orbitofrontal cortex encode economic value. Nature. 2006;441:223.
  67. 67.Grabenhorst F, Rolls ET. Value, pleasure and choice in the ventral prefrontal cortex. Trends Cogn Sci. 2011;15:56–67.
  68. 68.Furl N, Averbeck BB. Parietal cortex and insula relate to evidence seeking relevant to reward-related decisions. J Neurosci. 2011;31:17572–82.
  69. 69.Lambert NM, McLeod M, Schenk S. Subjective responses to initial experience with cocaine: an exploration of the incentive-sensitization theory of drug abuse. Addiction. 2006;101:713–25.
  70. 70.Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K, Schwarz L, et al. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell. 2015;162:622–34.
  71. 71.Ferenczi EA, Zalocusky KA, Liston C, Grosenick L, Warden MR, Amatya D, et al. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016;351:aac9698.
  72. 72.Taber MT, Das S, Fibiger HC. Cortical regulation of subcortical dopamine release: mediation via the ventral tegmental area. J Neurochemistry. 1995;65:1407–10.
  73. 73.Hayden BY, Platt ML. Neurons in anterior cingulate cortex multiplex information about reward and action. J Neurosci. 2010;30:3339–46.
  74. 74.Lodge DJ. The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function. Neuropsychopharmacology. 2011;36:1227.
  75. 75.Wu J, Gao M, Shen J-X, Shi W-X, Oster AM, Gutkin BS. Cortical control of VTA function and influence on nicotine reward. Biochem Pharmacol. 2013;86:1173–80.
  76. 76.Gaspar P, Berger B, Febvret A, Vigny A, Henry JP. Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase. J Comp Neurol. 1989;279:249–71.
  77. 77.Emson P, Koob G. The origin and distribution of dopamine-containing afferents to the rat frontal cortex. Brain Res. 1978;142:249–67.
  78. 78.Salamone JD. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation. Behavioural Brain Res. 1994;61:117–33.
  79. 79.Marshall DL, Redfern PH, Wonnacott S. Presynaptic nicotinic modulation of dopamine release in the three ascending pathways studied by in vivo microdialysis: comparison of naive and chronic nicotine‐treated rats. J Neurochemistry. 1997;68:1511–9.
  80. 80.Nisell M, Nomikos GG, Hertel P, Panagis G, Svensson TH. Condition‐independent sensitization of locomotor stimulation and mesocortical dopamine release following chronic nicotine treatment in the rat. Synapse. 1996;22:369–81.
  81. 81.Amiez C, Joseph JP, Procyk E. Anterior cingulate error‐related activity is modulated by predicted reward. Eur J Neurosci. 2005;21:3447–52.
  82. 82.Kennerley SW, Behrens TE, Wallis JD. Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat Neurosci. 2011;14:1581.
  83. 83.Brown JW, Braver TS. Learned predictions of error likelihood in the anterior cingulate cortex. Science. 2005;307:1118–21.
  84. 84.Hart AS, Rutledge RB, Glimcher PW, Phillips PE. Phasic dopamine release in the rat nucleus accumbens symmetrically encodes a reward prediction error term. J Neurosci. 2014;34:698–704.
  85. 85.Pagnoni G, Zink CF, Montague PR, Berns GS. Activity in human ventral striatum locked to errors of reward prediction. Nat Neurosci. 2002;5:97.
  86. 86.Day JJ, Roitman MF, Wightman RM, Carelli RM. Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens. Nat Neurosci. 2007;10:1020.
  87. 87.Wylie KP, Rojas DC, Tanabe J, Martin LF, Tregellas JR. Nicotine increases brain functional network efficiency. NeuroImage. 2012;63:73–80.
  88. 88.Falcone M, Cao W, Bernardo L, Tyndale RF, Loughead J, Lerman C. Brain responses to smoking cues differ based on nicotine metabolism rate. Biol Psychiatry. 2016;80:190–7.
  89. 89.Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD, et al. Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status. Biol Psychiatry. 2013;73:242–8.
  90. 90.Fluharty M, Taylor AE, Grabski M, Munafò MR. The association of cigarette smoking with depression and anxiety: a systematic review. Nicotine Tob Res. 2016;19:3–13.
  91. 91.Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ. 2014;348:g1151.

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Affiliations

  1. McLean Imaging Center, McLean Hospital, Belmont, MA, USA
    • Kainan S. Wang
    • , Maya Zegel
    • , Elena Molokotos
    • , Lauren V. Moran
    • , David P. Olson
    • , Diego A. Pizzagalli
    •  & Amy C. Janes
  2. Harvard Medical School, Boston, MA, USA
    • Kainan S. Wang
    • , Lauren V. Moran
    • , David P. Olson
    • , Diego A. Pizzagalli
    •  & Amy C. Janes
  3. Department of Psychology, Suffolk University, Boston, MA, USA
    • Elena Molokotos

Contributions

A.C.J. conceptualized and designed the study with DAP. M.Z. recruited and collected the data. K.S.W. conducted all analyses and wrote the initial draft with A.C.J. and E.M. L.V.M. and D.O. provided clinical expertise and served as study physicians. All authors reviewed and edited the final manuscript.

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Correspondence to Amy C. Janes.

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Wang, K.S., Zegel, M., Molokotos, E. et al. The acute effects of nicotine on corticostriatal responses to distinct phases of reward processing. Neuropsychopharmacol. (2020) doi:10.1038/s41386-020-0611-5

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