Abstract
Receptor imaging, including positron emission computed tomography (PET) and single photon emission computed tomography (SPECT), provides a way to measure chemicals of interest, such as receptors, and neurotransmitter fluctuations, in the living human brain. Imaging the neurochemical mechanisms involved in the maintenance and recovery from tobacco smoking has provided insights into critical smoking related brain adaptations. Nicotine, the primary addictive chemical in tobacco smoke, enters the brain, activates beta2-nicotinic acetylcholine receptors (β2*-nAChRs) and, like most drugs of abuse, elicits dopamine (DA) release in the ventral striatum. Both β2*-nAChRs and DA signaling are critical neurosubstrates underlying tobacco smoking behaviors and dependence and have been studied extensively with PET and SPECT brain imaging. We review the imaging literature on these topics and describe how brain imaging has helped inform the treatment of tobacco smoking.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abreu-Villaca Y, Seidler FJ, Qiao D, Tate CA, Cousins MM, Thillai I, Slotkin TA (2003) Short-term adolescent nicotine exposure has immediate and persistent effects on cholinergic systems: critical periods, patterns of exposure, dose thresholds. Neuropsychopharmacology 28:1935–1949
Barrett SP, Boileau I, Okker J, Pihl RO, Dagher A (2004) The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11C]raclopride. Synapse 54:65–71
Benwell M, Balfour D, Anderson J (1988) Evidence that tobacco smoking increases the density of (−)-[3H]nicotine binding site in human brain. J Neurochem 50:1243–1247
Breese C, Marks M, Logel J, Adams C, Sullivan B, Collins A, Leonard S (1997) Effect of smoking history on [3H]nicotine binding in human postmortem brain. J Pharmacol Exp Ther 282:7–13
Breese C, Lee M, Adams C, Sullivan B, Logel J, Gillen K, Marks M, Collins A, Leonard S (2000) Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 23:351–364
Brody AL, Olmstead RE, London ED (2004) Smoking-induced ventral striatum dopamine release. Am J Psychiatry 161:1211–1218
Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V, Tiongson E, Chefer SI, Koren AO, Mukhin AG (2006a) Cigarette smoking saturates brain alpha4 beta2 nicotinic acetylcholine receptors. Arch Gen Psychiatry 63:907–915
Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT (2006b) Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry 63:808–816
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 12:305–316
Brody AL, London ED, Olmstead RE, Allen-Martinez Z, Shulenberger S, Costello MR, Abrams AL, Scheibal D, Farahi J, Shoptaw S, Mandelkern MA (2010) Smoking-induced change in intrasynaptic dopamine concentration: effect of treatment for tobacco dependence. Psychiatry Res 183:218–224
Brody AL, Mandelkern MA, London ED, Khan A, Kozman D, Costello MR, Vellios EE, Archie MM, Bascom R, Mukhin AG (2012) Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain. Arch Gen Psychiatry 68:953–960
Brody AL, Mukhin AG, La Charite J, Ta K, Farahi J, Sugar CA, Mamoun MS, Vellios E, Archie M, Kozman M, Phuong J, Arlorio F, Mandelkern MA (2013a) Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers. Int J Neuropsychopharmacol 16:957–966
Brody AL, Mukhin AG, Stephanie S, Mamoun MS, Kozman M, Phuong J, Neary M, Luu T, Mandelkern MA (2013b) Treatment for tobacco dependence: effect on brain nicotinic acetylcholine receptor density. Neuropsychopharmacology 38:1548–1556
Brunzell DH, Boschen KE, Hendrick ES, Beardsley PM, McIntosh JM (2010) Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors in the nucleus accumbens shell regulate progressive ratio responding maintained by nicotine. Neuropsychopharmacology 35:665–673
Collins A, Romm E, Wehner J (1990) Dissociation of the apparent relationship between nicotine tolerance and up-regulation of nicotinic receptors. Brain Res Bull 25:373–379
Cosgrove KP, Batis J, Bois F, Maciejewski PK, Esterlis I, Kloczynski T, Stiklus S, Krishnan-Sarin S, O’Malley S, Perry E, Tamagnan G, Seibyl JP, Staley JK (2009) beta2-Nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking. Arch Gen Psychiatry 66:666–676
Cosgrove KP, Esterlis I, McKee S, Bois F, Alagille D, Tamagnan GD, Seibyl JP, Krishnan-Sarin S, Staley JK (2010) Beta2* nicotinic acetylcholine receptors modulate pain sensitivity in acutely abstinent tobacco smokers. Nicotine Tob Res 12:535–539
Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O’Malley SS (2012) Sex differences in availability of beta2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers. Arch Gen Psychiatry 69:418–427
D’Souza D, Esterlis I, Carbuto M, Krasenics M, Seibyl J, Bois F, Pittman B, Ranganathan M, Cosgrove K, Staley J (2012) Lower β2*-nicotinic acetylcholine receptor availability in smokers with schizophrenia. Am J Psychiatry 169:326–334
Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278
Epping-Jordan M, Picciotto M, Changeux J, Pich EM (1999) Assessment of nicotinic acetylcholine receptor subunit contributions to nicotine self-administration in mutant mice. Psychopharmacology 147:25–26
Esterlis I, Mitsis EM, Batis JC, Bois F, Picciotto MR, Stiklus SM, Kloczynski T, Perry E, Seibyl JP, McKee S, Staley JK, Cosgrove KP (2011) Brain beta2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler. Int J Neuropsychopharmacol 14:389–398
Esterlis I, Hannestad JO, Perkins E, Bois F, D’Souza DC, Tyndale RF, Seibyl JP, Hatsukami DM, Cosgrove KP, O’Malley SS (2013) Effect of a nicotine vaccine on nicotine binding to beta2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers. Am J Psychiatry 170:399–407
Girgis RR, Xu X, Miyake N, Easwaramoorthy B, Gunn RN, Rabiner EA, Abi-Dargham A, Slifstein M (2011) In vivo binding of antipsychotics to D(3) and D(2) receptors: a PET study in baboons with [(11)C]-(+)-PHNO. Neuropsychopharmacology 36:887–895
Imperato A, Mulas A, DiChiara G (1986) Nicotine preferentially stimulates dopamine release n the limbic system of freely moving rats. Eur J Pharmacol 132:337–338
Kassiou M, Eberl S, Meikle S, Birrell A, Constable C, Fulham M, Wong D, Musachio J (2001) In vivo imaging of nicotinic receptor upregulation following chronic (−)-nicotine treatment in baboon using SPECT. Nuc Med Biol 28:165–175
Kim SJ, Sullivan JM, Wang S, Cosgrove KP, Morris ED (2014) Voxelwise lp-ntPET for detecting localized, transient dopamine release of unknown timing: sensitivity analysis and application to cigarette smoking in the PET scanner. Hum Brain Mapp 35:4876–4891
Koranda JL, Cone JJ, McGehee DS, Roitman MF, Beeler JA, Zhuang X (2013) Nicotinic receptors regulate the dynamic range of dopamine release in vivo. J Neurophysiol 111:103–111
Koylu E, Demirgoren S, London E, Pogun S (1997) Sex difference in up-regulation of nicotinic acetylcholine receptors in rat brain. Life Sci 61:PL185–PL190
Laruelle M (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20:423–451
Le Foll B, Guranda M, Wilson AA, Houle S, Rusjan PM, Wing VC, Zawertailo L, Busto U, Selby P, Brody AL, George TP, Boileau I (2013) Elevation of dopamine induced by cigarette smoking: novel insights from a [(11)C]-(+)-PHNO PET study in humans. Neuropsychopharmacology 39:415–424
Mamede M, Ishizu K, Ueda M, Mukai T, Iida Y, Kawashima H, Fukuyama H, Togashi K, Saji H (2007) Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med 48:1829–1835
Marks MJ, Pauly JR, Gross SD, Deneris ES, Hermans-Borgmeyer I, Heinemann SF, Collins AC (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J Neurosci 12:2765–2784
Marubio LM, del Mar Arroyo-Jimenez M, Cordero-Erausquin M, Lena C, Le Novere N, de Kerchove d’Exaerde A, Huchet M, Damaj MI, Changeux JP (1999) Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 398:805–810
Mochizuki T, Villemagne V, Scheffel U, Dannals R, Finley P, Zhan Y, Wagner H, Musachio J (1998) Nicotine induced up-regulation of nicotinic receptors in CD-1 mice demonstrated with an in vivo radiotracer: gender differences. Synapse 30:116–118
Montgomery AJ, Lingford-Hughes AR, Egerton A, Nutt DJ, Grasby PM (2007) The effect of nicotine on striatal dopamine release in man: a [11C]raclopride PET study. Synapse 61:637–645
Morris ED, Kim SJ, Sullivan JM, Wang S, Normandin MD, Constantinescu CC, Cosgrove KP (2013) Creating dynamic images of short-lived dopamine fluctuations with lp-ntPET: dopamine movies of cigarette smoking. J Vis Exp 78
Mukhin AG, Kimes AS, Chefer SI, Matochik JA, Contoreggi CS, Horti AG, Vaupel DB, Pavlova O, Stein EA (2008) Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers: a PET study with 2-18F-FA-85380. J Nucl Med 49:1628–1635
Perkins KA (2009) Sex differences in nicotine reinforcement and reward: influences on the persistence of tobacco smoking. Nebr Symp Motiv 55:143–169
Perkins KA, Scott J (2008) Sex differences in long-term smoking cessation rates due to nicotine patch. Nicotine Tob Res 10:1245–1250
Perkins KA, Donny E, Caggiula AR (1999) Sex differences in nicotine effects and self-administration: review of human and animal evidence. Nicotine Tob Res 1:301–315
Picciotto M, Zoli M, Rimondin R, Lena C, Marubio L, Pich E, Fuxe K, Changeux J (1998) Acetycholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173–177
Pietila K, Lahde T, Attila M, Ahtee L, Nordberg A (1998) Regulation of nicotinic receptors in the brain of mice withdrawn from chronic oral nicotine treatment. Naunyn-Schmiedeberg’s Arch Pharmacol 357:176–182
Rose JE, Mukhin AG, Lokitz SJ, Turkington TG, Herskovic J, Behm FM, Garg S, Garg PK (2010) Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine. Proc Natl Acad Sci USA 107:5190–5195
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 32:450–457
Srinivasan R, Pantoja R, Moss FJ, Mackey ED, Son CD, Miwa J, Lester HA (2010) Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning. J Gen Physiol 137:59–79
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM, Tamagnan GD, Seibyl JP, Jatlow P, Picciotto MR, London ED, O’Malley S, van Dyck CH (2006) Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci 26:8707–8714
Sullivan JM, Kim SJ, Cosgrove KP, Morris ED (2013) Limitations of SRTM, Logan graphical method, and equilibrium analysis for measuring transient dopamine release with [(11)C]raclopride PET. Am J Nucl Med Mol Imaging 3:247–260
Takahashi H, Fujimura Y, Hayashi M, Takano H, Kato M, Okubo Y, Kanno I, Ito H, Suhara T (2008) Enhanced dopamine release by nicotine in cigarette smokers: a double-blind, randomized, placebo-controlled pilot study. Int J Neuropsychopharmacol 11:413–417
Tritto T, McCallum SE, Waddle SA, Hutton SR, Paylor R, Collins AC, Marks MJ (2004) Null mutant analysis of responses to nicotine: deletion of beta2 nicotinic acetylcholine receptor subunit but not alpha7 subunit reduces sensitivity to nicotine-induced locomotor depression and hypothermia. Nicotine Tob Res 6:145–158
Tziortzi AC, Searle GE, Tzimopoulou S, Salinas C, Beaver JD, Jenkinson M, Laruelle M, Rabiner EA, Gunn RN (2011) Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage 54:264–277
Acknowledgments
Funding K02 DA031750 (Cosgrove) and K01 MH092681 (Esterlis).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Cosgrove, K.P., Esterlis, I., Sandiego, C., Petrulli, R., Morris, E.D. (2015). Imaging Tobacco Smoking with PET and SPECT. In: Balfour, D., Munafò, M. (eds) The Neuropharmacology of Nicotine Dependence. Current Topics in Behavioral Neurosciences, vol 24. Springer, Cham. https://doi.org/10.1007/978-3-319-13482-6_1
Download citation
DOI: https://doi.org/10.1007/978-3-319-13482-6_1
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-13481-9
Online ISBN: 978-3-319-13482-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)