The Role of Mesoaccumbens Dopamine in Nicotine Dependence

Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 24)


There is abundant evidence that the dopamine (DA) neurons that project to the nucleus accumbens play a central role in neurobiological mechanisms underpinning drug dependence. This chapter considers the ways in which these projections facilitate the addiction to nicotine and tobacco. It focuses on the complimentary roles of the two principal subdivisions of the nucleus accumbens, the accumbal core and shell, in the acquisition and maintenance of nicotine-seeking behavior. The ways in which tonic and phasic firing of the neurons contributes to the ways in which the accumbens mediate the behavioral responses to nicotine are also considered. Experimental studies suggest that nicotine has relatively weak addictive properties which are insufficient to explain the powerful addictive properties of tobacco smoke. This chapter discusses hypotheses that seek to explain this conundrum. They implicate both discrete sensory stimuli closely paired with the delivery of tobacco smoke and contextual stimuli habitually associated with the delivery of the drug. The mechanisms by which each type of stimulus influence tobacco dependence are hypothesized to depend upon the increased DA release and overflow, respectively, in the two subdivisions of the accumbens. It is suggested that a majority of pharmacotherapies for tobacco dependence are not more successful because they fail to address this important aspect of the dependence.


Dopamine Extracellular Nucleus accumbens shell Nucleus accumbens core Conditioned stimuli Contextual conditioning 



The studies reported in this chapter from the author’s laboratory were performed with the aid of grants from the Wellcome Trust and Cancer Research UK.


  1. Alderson HL, Latimer MP, Winn P (2006) Intravenous self-administration of nicotine is altered by lesions of the posterior, but not anterior, pedunculopontine tegmental nucleus. Eur J Neurosci 23:2169–2175PubMedGoogle Scholar
  2. Aragona BJ, Cleaveland NA, Stuber GD, Day JJ, Carelli RM, Wightman RM (2008) Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. J Neurosci 28:8821–8831PubMedCentralPubMedGoogle Scholar
  3. Balfour DJ (2004) The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6:899–912PubMedGoogle Scholar
  4. Balfour DJ (2009) The neuronal pathways mediating the behavioral and addictive properties of nicotine. Hand Exp Pharmacol 192:209–233Google Scholar
  5. Balfour DJ, Birrell CE, Moran RJ, Benwell ME (1996) Effects of acute D-CPPene on mesoaccumbens dopamine responses to nicotine in the rat. Eur J Pharmacol 316:153–156PubMedGoogle Scholar
  6. Balfour DJ, Benwell ME, Birrell CE, Kelly RJ, Al-Aloul M (1998) Sensitization of the mesoaccumbens dopamine response to nicotine. Pharmacol Biochem Behav 59:1021–1030PubMedGoogle Scholar
  7. 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 113:73–83PubMedGoogle Scholar
  8. Bassareo V, De Luca MA, Di Chiara G (2007) Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex. Psychopharmacology 191:689–703PubMedGoogle Scholar
  9. Beard E, McNeill A, Aveyard P, Fidler J, Michie S, West R (2013) Association between use of nicotine replacement therapy for harm reduction and smoking cessation: a prospective study of English smokers. Tob Control 22:118–122PubMedGoogle Scholar
  10. Benwell ME, Balfour DJ (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856PubMedCentralPubMedGoogle Scholar
  11. Benwell ME, Balfour DJ (1997) Regional variation in the effects of nicotine on catecholamine overflow in rat brain. Eur J Pharmacol 325:13–20PubMedGoogle Scholar
  12. Benwell ME, Balfour DJ, Birrell CE (1995) Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine. Br J Pharmacol 114:454–460PubMedCentralPubMedGoogle Scholar
  13. Benwell ME, Holtom PE, Moran RJ, Balfour DJ (1996) Neurochemical and behavioural interactions between ibogaine and nicotine in the rat. Br J Pharmacol 117:743–749PubMedCentralPubMedGoogle Scholar
  14. Benowitz NC, Porcheth, Jacob P (1990) Pharmacokinetics metabolism and pharmacodynamics of nicotine. In: Wonnacott S, Russell MAH, Stolerman IP (eds). Niconne psychopharmacology: molecular cellular and behavioural aspects. Oxford University Press, Oxford, pp 112–157Google Scholar
  15. Bespalov AY, Dravolina OA, Sukhanov I, Zakharova E, Blokhina E, Zvartau E, Danysz W, van Heeke G, Markou A (2005) Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats. Neuropharmacology 491:167–178PubMedGoogle Scholar
  16. Bevins RA, Palmatier MI (2003) Nicotine-conditioned locomotor sensitization in rats: assessment of the US-preexposure effect. Behav Brain Res 143:65–74PubMedGoogle Scholar
  17. Birrell CE, Balfour DJ (1998) The influence of nicotine pretreatment on mesoaccumbens dopamine overflow and locomotor responses to D-amphetamine. Psychopharmacology 140:142–149PubMedGoogle Scholar
  18. Bossert JM, Poles GC, Wihbey KA, Koya E, Shaham Y (2007) Differential effects of blockade of dopamine D1-family receptors in nucleus accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues. J Neurosci 27:12655–12663PubMedCentralPubMedGoogle Scholar
  19. Boye SM, Grant RJ, Clarke PB (2001) Disruption of dopaminergic neurotransmission in nucleus accumbens core inhibits the locomotor stimulant effects of nicotine and D-amphetamine in rats. Neuropharmacology 40:792–805PubMedGoogle Scholar
  20. Bozarth MA, Wise RA (1984) Anatomically distinct opiate receptor fields mediate reward and physical dependence. Science 224:516–517PubMedGoogle Scholar
  21. Brauer LH, Behm FM, Lane JD, Westman EC, Perkins C, Rose JE (2001) Individual differences in smoking reward from de-nicotinized cigarettes. Nicotine Tob Res 3:101–109PubMedGoogle Scholar
  22. Brazell MP, Mitchell SN, Joseph MH, Gray JA (1990) Acute administration of nicotine increases the in vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen. Neuropharmacology 29:1177–1185PubMedGoogle Scholar
  23. Brody AL (2006) Functional brain imaging of tobacco use and dependence. J Psychiatr Res 40:404–418PubMedCentralPubMedGoogle Scholar
  24. Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, Hahn EL, Mandelkern MA (2004) Smoking-induced ventral striatum dopamine release. Am J Psychiatry 161:1211–1218PubMedGoogle Scholar
  25. 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 183:218–224PubMedCentralPubMedGoogle Scholar
  26. Brower VG, Fu Y, Matta SG, Sharp BM (2002) Rat strain differences in nicotine self-administration using an unlimited access paradigm. Brain Res 930:12–20PubMedGoogle Scholar
  27. Bruijnzeel AW, Markou A (2004) Adaptations in cholinergic transmission in the ventral tegmental area associated with the affective signs of nicotine withdrawal in rats. Neuropharmacology 47:572–579PubMedGoogle Scholar
  28. Cadoni C, Di Chiara G (1999) Reciprocal changes in dopamine responsiveness in the nucleus accumbens shell and core and in the dorsal caudate-putamen in rats sensitized to morphine. Neuroscience 90:447–455PubMedGoogle Scholar
  29. Cadoni C, Di Chiara G (2000) Differential changes in accumbens shell and core dopamine in behavioral sensitization to nicotine. Eur J Pharmacol 387:R23–R25PubMedGoogle Scholar
  30. Cadoni C, Solinas M, Di Chiara G (2000) Psychostimulant sensitization: differential changes in accumbal shell and core dopamine. Eur J Pharmacol 388:69–76PubMedGoogle Scholar
  31. Cadoni C, Muto T, Di Chiara G (2009) Nicotine differentially affects dopamine transmission in the nucleus accumbens shell and core of Lewis and Fischer 344 rats. Neuropharmacology 57:496–501PubMedGoogle Scholar
  32. 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 70:515–530PubMedGoogle Scholar
  33. Caggiula AR, Donny EC, Chaudhri N, Perkins KA, Evans-Martin FF, Sved AF (2002) Importance of nonpharmacological factors in nicotine self-administration. Physiol Behav 77:683–687PubMedGoogle Scholar
  34. Cahill K, Stead LF, Lancaster T (2012) Nicotine receptor partial agonists for smoking cessation. The Cochrane database of systematic reviews 4: CD006103Google Scholar
  35. Cahill K, Stevens S, Perera R, Lancaster T (2013) Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 5:CD009329Google Scholar
  36. Cannon CM, Palmiter RD (2003) Reward without dopamine. J Neurosci 23:10827–10831PubMedGoogle Scholar
  37. Caponnetto P, Campagna D, Papale G, Russo C, Polosa R (2012) The emerging phenomenon of electronic cigarettes. Exp Rev Resp Med 6:63–74Google Scholar
  38. Carboni E, Bortone L, Giua C, Di Chiara G (2000) Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats. Drug Alcohol Depend 58:93–102PubMedGoogle Scholar
  39. Chaudhri N, Caggiula AR, Donny EC, Palmatier MI, Liu X, Sved AF (2006) Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement. Psychopharmacology 184:353–366PubMedGoogle Scholar
  40. Chaudhri N, Sahuque LL, Schairer WW, Janak PH (2010) Separable roles of the nucleus accumbens core and shell in context—and cue-induced alcohol-seeking. Neuropsychopharmacology 35:783–791PubMedCentralPubMedGoogle Scholar
  41. Chergui K, Charlety PJ, Akaoka H, Saunier CF, Brunet JL, Buda M, Svensson TH, Chouvet G (1993) Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo. Eur J Neurosci 5:137–144PubMedGoogle Scholar
  42. Clarke PB, Kumar R (1983) The effects of nicotine on locomotor activity in non-tolerant and tolerant rats. Br J Pharmacol 78:329–337PubMedCentralPubMedGoogle Scholar
  43. Clarke PB, Fu DS, Jakubovic A, Fibiger HC (1988) Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats. J Pharmacol Exp Ther 246:701–708PubMedGoogle Scholar
  44. Coen KM, Adamson KL, Corrigall WA (2009) Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement. Psychopharmacology 201:557–568PubMedGoogle Scholar
  45. Cohen C, Perrault G, Voltz C, Steinberg R, Soubrie P (2002) SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 13:451–463PubMedGoogle Scholar
  46. Cohen C, Kodas E, Griebel G (2005) CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav 81:387–395PubMedGoogle Scholar
  47. Corrigall WA, Coen KM (1989) Nicotine maintains robust self-administration in rats on a limited-access schedule. Psychopharmacology 99:473–478PubMedGoogle Scholar
  48. Corrigall WA, Franklin KB, Coen KM, Clarke PB (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology 107:285–289PubMedGoogle Scholar
  49. Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653:278–284PubMedGoogle Scholar
  50. Corrigall WA, Coen KM, Zhang J, Adamson KL (2001) GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat. Psychopharmacology 158:190–197PubMedGoogle Scholar
  51. Corrigall WA, Coen KM, Zhang J, Adamson L (2002) Pharmacological manipulations of the pedunculopontine tegmental nucleus in the rat reduce self-administration of both nicotine and cocaine. Psychopharmacology 160:198–205PubMedGoogle Scholar
  52. Crippens D, Robinson TE (1994) Withdrawal from morphine or amphetamine: different effects on dopamine in the ventral-medial striatum studied with microdialysis. Brain Res 650:56–62PubMedGoogle Scholar
  53. Crippens D, Camp DM, Robinson TE (1993) Basal extracellular dopamine in the nucleus accumbens during amphetamine withdrawal: a ‘no net flux’ microdialysis study. Neurosci Lett 164:145–148PubMedGoogle Scholar
  54. Crombag HS, Bossert JM, Koya E, Shaham Y (2008) Context-induced relapse to drug seeking: a review. Philos Trans R Soc Biol Sci 363:3233–3243Google Scholar
  55. Cryan JF, Hoyer D, Markou A (2003) Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 54:49–58PubMedGoogle Scholar
  56. Dackis CA, Gold MS (1985) New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 9:469–477PubMedGoogle Scholar
  57. Dagher A, Bleicher C, Aston JA, Gunn RN, Clarke PB, Cumming P (2001) Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers. Synapse 42:48–53PubMedGoogle Scholar
  58. Damsma G, Day J, Fibiger HC (1989) Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens. Eur J Pharmacol 168:363–368PubMedGoogle Scholar
  59. Dawe S, Gerada C, Russell MA, Gray JA (1995) Nicotine intake in smokers increases following a single dose of haloperidol. Psychopharmacology 117:110–115PubMedGoogle Scholar
  60. Di Chiara G (1995) The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38:95–137PubMedGoogle Scholar
  61. Di Chiara G (1999) Drug addiction as dopamine-dependent associative learning disorder. Eur J Pharmacol 375:13–30PubMedGoogle Scholar
  62. Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314PubMedGoogle Scholar
  63. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114PubMedGoogle Scholar
  64. Di Chiara G, Bassareo V (2007) Reward system and addiction: what dopamine does and doesn’t do. Curr Opin Pharmacol 7:69–76PubMedGoogle Scholar
  65. 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 85:5274–5278Google Scholar
  66. Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004) Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47:227–241PubMedGoogle Scholar
  67. Diergaarde L, de Vries W, Raaso H, Schoffelmeer AN, De Vries TJ (2008) Contextual renewal of nicotine seeking in rats and its suppression by the cannabinoid-1 receptor antagonist Rimonabant (SR141716A). Neuropharmacology 55:712–716PubMedGoogle Scholar
  68. Dockrell M, Morrison R, Bauld L, McNeill A (2013) E-cigarettes: prevalence and attitudes in Great Britain. Nicotine Tob Res 15:1737–1744PubMedCentralPubMedGoogle Scholar
  69. 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 169:68–76PubMedGoogle Scholar
  70. D’Souza MS, Markou A (2010) Neural substrates of psychostimulant withdrawal-induced anhedonia. Curr Top Behav Neurosci 3:119–178PubMedGoogle Scholar
  71. D’Souza MS, Markou A (2011) Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) microinfusions into the nucleus accumbens shell or ventral tegmental area attenuate the reinforcing effects of nicotine in rats. Neuropharmacology 61:1399–1405PubMedCentralPubMedGoogle Scholar
  72. D’Souza MS, Markou A (2014) Differential role of N-methyl-D-aspartate receptor-mediated glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats. Eur J NeurosciGoogle Scholar
  73. Epping-Jordan MP, Watkins SS, Koob GF, Markou A (1998) Dramatic decreases in brain reward function during nicotine withdrawal. Nature 393:76–79PubMedGoogle Scholar
  74. Etter JF, Bullen C (2011) Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy. Addiction 106:2017–2028PubMedGoogle Scholar
  75. Fagen ZM, Mansvelder HD, Keath JR, McGehee DS (2003) Short- and long-term modulation of synaptic inputs to brain reward areas by nicotine. Ann NY Acad Sci 1003:185–195PubMedGoogle Scholar
  76. Fagerstrom K, Eissenberg T (2012) Dependence on tobacco and nicotine products: a case for product-specific assessment. Nicotine Tob Res 14:1382–1390PubMedCentralPubMedGoogle Scholar
  77. Farquhar MJ, Latimer MP, Winn P (2012) Nicotine self-administered directly into the VTA by rats is weakly reinforcing but has strong reinforcement enhancing properties. Psychopharmacology 220:43–54PubMedGoogle Scholar
  78. Floresco SB (2007) Dopaminergic regulation of limbic-striatal interplay. Journal Psychiatry Neurosci 32:400–411Google Scholar
  79. Floresco SB, Todd CL, Grace AA (2001) Glutamatergic afferents from the hippocampus to the nucleus accumbens regulate activity of ventral tegmental area dopamine neurons. J Neurosci 21:4915–4922PubMedGoogle Scholar
  80. Floresco SB, West AR, Ash B, Moore H, Grace AA (2003) Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6:968–973PubMedGoogle Scholar
  81. Floresco SB, St Onge JR, Ghods-Sharifi S, Winstanley CA (2008) Cortico-limbic-striatal circuits subserving different forms of cost-benefit decision making. Cogn Affect Behav Neurosci 8:375–389PubMedGoogle Scholar
  82. Fowler JS, Logan J, Wang GJ, Volkow ND (2003) Monoamine oxidase and cigarette smoking. Neurotoxicology 24:75–82PubMedGoogle Scholar
  83. Fu Y, Matta SG, Gao W, Brower VG, Sharp BM (2000) Systemic nicotine stimulates dopamine release in nucleus accumbens: re-evaluation of the role of N-methyl-D-aspartate receptors in the ventral tegmental area. J Pharmacol Exp Ther 294:458–465PubMedGoogle Scholar
  84. Fuxe K, Dahlstrom AB, Jonsson G, Marcellino D, Guescini M, Dam M, Manger P, Agnati L (2010) The discovery of central monoamine neurons gave volume transmission to the wired brain. Prog Neurobiol 90:82–100PubMedGoogle Scholar
  85. Garris PA, Wightman RM (1994) Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study. J Neurosci 14:442–450PubMedGoogle Scholar
  86. Gerrits MA, Van Ree JM (1996) Effect of nucleus accumbens dopamine depletion on motivational aspects involved in initiation of cocaine and heroin self-administration in rats. Brain Res 713:114–124PubMedGoogle Scholar
  87. Glick SD, Maisonneuve IM (2000) Development of novel medications for drug addiction. The legacy of an African shrub. Ann NY Acad Sci 909:88–103PubMedGoogle Scholar
  88. Gold MS, Dackis CA (1984) New insights and treatments: opiate withdrawal and cocaine addiction. Clin Ther 7:6–21PubMedGoogle Scholar
  89. Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1–24PubMedGoogle Scholar
  90. Grace AA (2000) The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction 95:S119–S128PubMedGoogle Scholar
  91. Grace AA, Bunney BS (1984a) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4:2877–2890PubMedGoogle Scholar
  92. Grace AA, Bunney BS (1984b) The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci 4:2866–2876PubMedGoogle Scholar
  93. Grace AA, Floresco SB, Goto Y, Lodge DJ (2007) Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci 30:220–227PubMedGoogle Scholar
  94. Grenhoff J, Aston-Jones G, Svensson TH (1986) Nicotinic effects on the firing pattern of midbrain dopamine neurons. Acta Physiol Scand 128:351–358PubMedGoogle Scholar
  95. Grieder TE, George O, Tan H, George SR, Le Foll B, Laviolette SR, van der Kooy D (2012) Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal. Proc Natl Acad Sci USA 109:3101–3106Google Scholar
  96. Guillem K, Vouillac C, Azar MR, Parsons LH, Koob GF, Cador M, Stinus L (2005) Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats. J Neurosci 25:8593–8600PubMedGoogle Scholar
  97. Guillem K, Vouillac C, Azar MR, Parsons LH, Koob GF, Cador M, Stinus L (2006) Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats. Eur J Neurosci 24:3532–3540PubMedGoogle Scholar
  98. Hajek P, McRobbie H, Myers K (2013) Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax 68:1037–1042PubMedGoogle Scholar
  99. Hashimoto K, Malchow B, Falkai P, Schmitt A (2013) Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci 263:367–377PubMedGoogle Scholar
  100. Heien ML, Wightman RM (2006) Phasic dopamine signaling during behavior, reward, and disease states. CNS Neurol Disord: Drug Targets 5:99–108Google Scholar
  101. Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125PubMedGoogle Scholar
  102. Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI (1997) Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra. J Comp Neurol 388:211–227PubMedGoogle Scholar
  103. Hildebrand BE, Svensson TH (2000) Intraaccumbal mecamylamine infusion does not affect dopamine output in the nucleus accumbens of chronically nicotine-treated rats. J Neural Transm 107:861–872PubMedGoogle Scholar
  104. Hildebrand BE, Nomikos GG, Bondjers C, Nisell M, Svensson TH (1997) Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms. Psychopharmacology 129:348–356PubMedGoogle Scholar
  105. Hildebrand BE, Nomikos GG, Hertel P, Schilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779:214–225PubMedGoogle Scholar
  106. Hollander JA, Carelli RM (2007) Cocaine-associated stimuli increase cocaine seeking and activate accumbens core neurons after abstinence. J Neurosci 27:3535–3539PubMedGoogle Scholar
  107. Ikemoto S (2003) Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies. J Neurosci 23:9305–9311PubMedGoogle Scholar
  108. Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. Eur J Pharmacol 132:337–338PubMedGoogle Scholar
  109. Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20:7489–7495PubMedGoogle Scholar
  110. Ito R, Dalley JW, Robbins TW, Everitt BJ (2002) Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue. J Neurosci 22:6247–6253PubMedGoogle Scholar
  111. Ito R, Robbins TW, Everitt BJ (2004) Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci 7:389–397PubMedGoogle Scholar
  112. Ito R, Robbins TW, Pennartz CM, Everitt BJ (2008) Functional interaction between the hippocampus and nucleus accumbens shell is necessary for the acquisition of appetitive spatial context conditioning. J Neurosci 28:6950–6959PubMedCentralPubMedGoogle Scholar
  113. Iyaniwura TT, Wright AE, Balfour DJ (2001) Evidence that mesoaccumbens dopamine and locomotor responses to nicotine in the rat are influenced by pretreatment dose and strain. Psychopharmacology 158:73–79PubMedGoogle Scholar
  114. Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, Bentley B (2002) Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation. Drugs 62:11–24PubMedGoogle Scholar
  115. Jones SR, O’Dell SJ, Marshall JF, Wightman RM (1996) Functional and anatomical evidence for different dopamine dynamics in the core and shell of the nucleus accumbens in slices of rat brain. Synapse 23:224–231PubMedGoogle Scholar
  116. Keck TM, Yang HJ, Bi GH, Huang Y, Zhang HY, Srivastava R, Gardner EL, Newman AH, Xi ZX (2013) Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in rats: implications for addiction treatment in humans. Psychopharmacology 229:253–265PubMedCentralPubMedGoogle Scholar
  117. Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 70:531–549PubMedGoogle Scholar
  118. Kenny PJ, Paterson NE, Boutrel B, Semenova S, Harrison AA, Gasparini F, Koob GF, Skoubis PD, Markou A (2003) Metabotropic glutamate 5 receptor antagonist MPEP decreased nicotine and cocaine self-administration but not nicotine and cocaine-induced facilitation of brain reward function in rats. Ann NY Acad Sci 1003:415–418PubMedGoogle Scholar
  119. Kenny PJ, Chartoff E, Roberto M, Carlezon WA Jr, Markou A (2009) NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala. Neuropsychopharmacology 34:266–281PubMedCentralPubMedGoogle Scholar
  120. Kraiczi H, Hansson A, Perfekt R (2011) Single-dose pharmacokinetics of nicotine when given with a novel mouth spray for nicotine replacement therapy. Nicotine Tob Res 13:1176–1182PubMedGoogle Scholar
  121. Kyerematen GA, Taylor LH, deBethizy JD, Vesell ES (1988) Pharmacokinetics of nicotine and 12 metabolites in the rat. Application of a new radiometric high performance liquid chromatography assay. Drug Metab Dispos 16:125–129PubMedGoogle Scholar
  122. Lanca AJ, Adamson KL, Coen KM, Chow BL, Corrigall WA (2000) The pedunculopontine tegmental nucleus and the role of cholinergic neurons in nicotine self-administration in the rat: a correlative neuroanatomical and behavioral study. Neuroscience 96:735–742PubMedGoogle Scholar
  123. Le Foll B, Goldberg SR (2005) Control of the reinforcing effects of nicotine by associated environmental stimuli in animals and humans. Trends Pharmacol Sci 26:287–293PubMedGoogle Scholar
  124. Lecca D, Cacciapaglia F, Valentini V, Gronli J, Spiga S, Di Chiara G (2006) Preferential increase of extracellular dopamine in the rat nucleus accumbens shell as compared to that in the core during acquisition and maintenance of intravenous nicotine self-administration. Psychopharmacology 184:435–446PubMedGoogle Scholar
  125. Lecca D, Cacciapaglia F, Valentini V, Acquas E, Di Chiara G (2007a) Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat. Psychopharmacology 191:653–667PubMedGoogle Scholar
  126. Lecca D, Valentini V, Cacciapaglia F, Acquas E, Di Chiara G (2007b) Reciprocal effects of response contingent and noncontingent intravenous heroin on in vivo nucleus accumbens shell versus core dopamine in the rat: a repeated sampling microdialysis study. Psychopharmacology 194:103–116PubMedGoogle Scholar
  127. Legault M, Wise RA (1999) Injections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens. Synapse 31:241–249PubMedGoogle Scholar
  128. 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 170:278–286PubMedGoogle Scholar
  129. LeSage MG, Burroughs D, Dufek M, Keyler DE, Pentel PR (2004) Reinstatement of nicotine self-administration in rats by presentation of nicotine-paired stimuli, but not nicotine priming. Pharmacol Biochem Behav 79:507–513PubMedGoogle Scholar
  130. Li W, Doyon WM, Dani JA (2011) Acute in vivo nicotine administration enhances synchrony among dopamine neurons. Biochem Pharmacol 82:977–983PubMedCentralPubMedGoogle Scholar
  131. Livingstone PD, Wonnacott S (2009) Nicotinic acetylcholine receptors and the ascending dopamine pathways. Biochem Pharmacol 78:744–755PubMedGoogle Scholar
  132. Lodge DJ, Grace AA (2006a) The hippocampus modulates dopamine neuron responsivity by regulating the intensity of phasic neuron activation. Neuropsychopharmacology 31:1356–1361PubMedGoogle Scholar
  133. Lodge DJ, Grace AA (2006b) The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons. Proc Natl Acad Sci USA 103:5167–5172Google Scholar
  134. Louis M, Clarke PB (1998) Effect of ventral tegmental 6-hydroxydopamine lesions on the locomotor stimulant action of nicotine in rats. Neuropharmacology 37:1503–1513PubMedGoogle Scholar
  135. Lu XY, Ghasemzadeh MB, Kalivas PW (1999) Expression of glutamate receptor subunit/subtype messenger RNAS for NMDAR1, GLuR1, GLuR2 and mGLuR5 by accumbal projection neurons. Brain Res Mol Brain Res 63:287–296PubMedGoogle Scholar
  136. Lyness WH, Friedle NM, Moore KE (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556PubMedGoogle Scholar
  137. Malin DH (2001) Nicotine dependence: studies with a laboratory model. Pharmacol Biochem Behav 70:551–559PubMedGoogle Scholar
  138. Malin DH, Goyarzu P (2009) Rodent models of nicotine withdrawal syndrome. Handb Exp Pharmacol 192:401–434PubMedGoogle Scholar
  139. Malin DH, Lake JR, Newlin-Maultsby P, Roberts LK, Lanier JG, Carter VA, Cunningham JS, Wilson OB (1992) Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav 43:779–784PubMedGoogle Scholar
  140. Malin DH, Lake JR, Carter VA, Cunningham JS, Hebert KM, Conrad DL, Wilson OB (1994) The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat. Psychopharmacology 115:180–184PubMedGoogle Scholar
  141. Malin DH, Lake JR, Smith TD, Khambati HN, Meyers-Paal RL, Montellano AL, Jennings RE, Erwin DS, Presley SE, Perales BA (2006) Bupropion attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 184:494–503PubMedGoogle Scholar
  142. Mameli-Engvall M, Evrard A, Pons S, Maskos U, Svensson TH, Changeux JP, Faure P (2006) Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron 50:911–921PubMedGoogle Scholar
  143. Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27:349–357PubMedGoogle Scholar
  144. Mansvelder HD, McGehee DS (2002) Cellular and synaptic mechanisms of nicotine addiction. J Neurobiol 53:606–617PubMedGoogle Scholar
  145. Mansvelder HD, Keath JR, McGehee DS (2002) Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 33:905–919PubMedGoogle Scholar
  146. Markou A (2008) Review. Neurobiology of nicotine dependence. Philos Trans R Soc Lond B Biol Sci 363:3159–3168PubMedCentralPubMedGoogle Scholar
  147. Markou A, Koob GF (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26PubMedGoogle Scholar
  148. Mascia P, Pistis M, Justinova Z, Panlilio LV, Luchicchi A, Lecca S, Scherma M, Fratta W, Fadda P, Barnes C, Redhi GH, Yasar S, Le Foll B, Tanda G, Piomelli D, Goldberg SR (2011) Blockade of nicotine reward and reinstatement by activation of alpha-type peroxisome proliferator-activated receptors. Biol Psychiatry 69:633–641PubMedCentralPubMedGoogle Scholar
  149. Mereu G, Yoon KW, Boi V, Gessa GL, Naes L, Westfall TC (1987) Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine. Eur J Pharmacol 141:395–399PubMedGoogle Scholar
  150. Mihalak KB, Carroll FI, Luetje CW (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 70:801–805PubMedGoogle Scholar
  151. Nirenberg MJ, Chan J, Pohorille A, Vaughan RA, Uhl GR, Kuhar MJ, Pickel VM (1997) The dopamine transporter: comparative ultrastructure of dopaminergic axons in limbic and motor compartments of the nucleus accumbens. J Neurosci 17:6899–6907PubMedGoogle Scholar
  152. Nisell M, Nomikos GG, Svensson TH (1994a) Infusion of nicotine in the ventral tegmental area or the nucleus accumbens of the rat differentially affects accumbal dopamine release. Pharmacol Toxicol 75:348–352PubMedGoogle Scholar
  153. Nisell M, Nomikos GG, Svensson TH (1994b) Systemic nicotine-induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area. Synapse 16:36–44PubMedGoogle Scholar
  154. Nunes EJ, Randall PA, Podurgiel S, Correa M, Salamone JD (2013) Nucleus accumbens neurotransmission and effort-related choice behavior in food motivation: effects of drugs acting on dopamine, adenosine, and muscarinic acetylcholine receptors. Neurosci Biobehav Rev 37:2015–2025PubMedGoogle Scholar
  155. O’Connor EC, Parker D, Rollema H, Mead AN (2010) The alpha4beta2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology 208:365–376PubMedGoogle Scholar
  156. O’Dell LE, Khroyan TV (2009) Rodent models of nicotine reward: what do they tell us about tobacco abuse in humans? Pharmacol Biochem Behav 91:481–488PubMedCentralPubMedGoogle Scholar
  157. Owesson-White CA, Roitman MF, Sombers LA, Belle AM, Keithley RB, Peele JL, Carelli RM, Wightman RM (2012) Sources contributing to the average extracellular concentration of dopamine in the nucleus accumbens. J Neurochem 121:252–262PubMedCentralPubMedGoogle Scholar
  158. Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, Donny EC, Liu X, Booth S, Gharib M, Craven L, Sved AF (2006) Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers. Psychopharmacology 184:391–400PubMedGoogle Scholar
  159. Palmatier MI, Matteson GL, Black JJ, Liu X, Caggiula AR, Craven L, Donny EC, Sved AF (2007) The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections. Drug Alcohol Depend 89:52–59PubMedCentralPubMedGoogle Scholar
  160. Palmatier MI, Liu X, Donny EC, Caggiula AR, Sved AF (2008) Metabotropic glutamate 5 receptor (mGluR5) antagonists decrease nicotine seeking, but do not affect the reinforcement enhancing effects of nicotine. Neuropsychopharmacology 33:2139–2147PubMedCentralPubMedGoogle Scholar
  161. Panagis G, Nisell M, Nomikos GG, Chergui K, Svensson TH (1996) Nicotine injections into the ventral tegmental area increase locomotion and Fos-like immunoreactivity in the nucleus accumbens of the rat. Brain Res 730:133–142PubMedGoogle Scholar
  162. Paterson NE, Markou A (2004) Prolonged nicotine dependence associated with extended access to nicotine self-administration in rats. Psychopharmacology 173:64–72PubMedGoogle Scholar
  163. Paterson NE, Markou A (2005) The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats. Psychopharmacology 179:255–261PubMedGoogle Scholar
  164. Paterson NE, Markou A (2007) Animal models and treatments for addiction and depression co-morbidity. Neurotox Res 11:1–32PubMedGoogle Scholar
  165. Paterson NE, Semenova S, Gasparini F, Markou A (2003) The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice. Psychopharmacology 167:257–264PubMedGoogle Scholar
  166. Paterson NE, Balfour DJ, Markou A (2007) Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell. Eur J Neurosci 25:3099–3108PubMedGoogle Scholar
  167. Paterson NE, Min W, Hackett A, Lowe D, Hanania T, Caldarone B, Ghavami A (2010) The high-affinity nAChR partial agonists varenicline and sazetidine-A exhibit reinforcing properties in rats. Prog Neuropsychopharmacol Biol Psychiatry 34:1455–1464PubMedGoogle Scholar
  168. Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 84:167–173PubMedGoogle Scholar
  169. Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422:614–618PubMedGoogle Scholar
  170. Pidoplichko VI, DeBiasi M, Williams JT, Dani JA (1997) Nicotine activates and desensitizes midbrain dopamine neurons. Nature 390:401–404PubMedGoogle Scholar
  171. Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257PubMedGoogle Scholar
  172. Rada P, Jensen K, Hoebel BG (2001) Effects of nicotine and mecamylamine-induced withdrawal on extracellular dopamine and acetylcholine in the rat nucleus accumbens. Psychopharmacology 157:105–110PubMedGoogle Scholar
  173. Ranaldi R, Roberts DC (1996) Initiation, maintenance and extinction of cocaine self-administration with and without conditioned reward. Psychopharmacology 128:89–96PubMedGoogle Scholar
  174. Rauhut AS, Neugebauer N, Dwoskin LP, Bardo MT (2003) Effect of bupropion on nicotine self-administration in rats. Psychopharmacology 169:1–9PubMedGoogle Scholar
  175. Reavill C, Walther B, Stolerman IP, Testa B (1990) Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline. Neuropharmacology 29:619–624PubMedGoogle Scholar
  176. Reid MS, Ho LB, Berger SP (1998) Behavioral and neurochemical components of nicotine sensitization following 15-day pretreatment: studies on contextual conditioning. Behav Pharmacol 9:137–148PubMedGoogle Scholar
  177. Reperant C, Pons S, Dufour E, Rollema H, Gardier AM, Maskos U (2010) Effect of the alpha4beta2* nicotinic acetylcholine receptor partial agonist varenicline on dopamine release in beta2 knock-out mice with selective re-expression of the beta2 subunit in the ventral tegmental area. Neuropharmacology 58:346–350PubMedGoogle Scholar
  178. Roberts DC, Koob GF (1982) Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol Biochem Behav 17:901–904PubMedGoogle Scholar
  179. Roberts DC, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620PubMedGoogle Scholar
  180. Rocha BA, Fumagalli F, Gainetdinov RR, Jones SR, Ator R, Giros B, Miller GW, Caron MG (1998) Cocaine self-administration in dopamine-transporter knockout mice. Nat Neurosci 1:132–137PubMedGoogle Scholar
  181. Rodd-Henricks ZA, McKinzie DL, Li TK, Murphy JM, McBride WJ (2002) Cocaine is self-administered into the shell but not the core of the nucleus accumbens of Wistar rats. J Pharmacol Exp Ther 303:1216–1226PubMedGoogle Scholar
  182. Rodriguez AL, Tarr JC, Zhou Y, Williams R, Gregory KJ, Bridges TM, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR (2010) Identification of a glycine sulfonamide based non-MPEP site positive allosteric potentiator (PAM) of mGlu5 probe reports from the NIH molecular libraries program, Bethesda (MD)Google Scholar
  183. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley FD 3rd, Williams KE (2007a) Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology 52:985–994PubMedGoogle Scholar
  184. Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE (2007b) Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. Trends Pharmacol Sci 28:316–325PubMedGoogle Scholar
  185. Rollema H, Shrikhande A, Ward KM, Tingley FD 3rd, Coe JW, O’Neill BT, Tseng E, Wang EQ, Mather RJ, Hurst RS, Williams KE, de Vries M, Cremers T, Bertrand S, Bertrand D (2010) Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. Br J Pharmacol 160:334–345PubMedCentralPubMedGoogle Scholar
  186. Rose JE (2006) Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology 184:274–285PubMedGoogle Scholar
  187. Rose JE, Behm FM, Westman EC, Johnson M (2000) Dissociating nicotine and nonnicotine componenents of cigarette smoking. Pharmacol Biochem Behav 67:71–78Google Scholar
  188. Salamone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76:470–485PubMedGoogle Scholar
  189. Salamone JD, Correa M (2013) Dopamine and food addiction: lexicon badly needed. Biol Psychiatry 73:e15–e24PubMedGoogle Scholar
  190. Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191:461–482PubMedGoogle Scholar
  191. Salamone JD, Correa M, Nunes EJ, Randall PA, Pardo M (2012) The behavioral pharmacology of effort-related choice behavior: dopamine, adenosine and beyond. J Exp Anal Behav 97:125–146PubMedCentralPubMedGoogle Scholar
  192. Saura J, Kettler R, Da Prada M, Richards JG (1992) Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci 12:1977–1999PubMedGoogle Scholar
  193. Scherma M, Panlilio LV, Fadda P, Fattore L, Gamaleddin I, Le Foll B, Justinova Z, Mikics E, Haller J, Medalie J, Stroik J, Barnes C, Yasar S, Tanda G, Piomelli D, Fratta W, Goldberg SR (2008) Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3′-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther 327:482–490PubMedCentralPubMedGoogle Scholar
  194. Scherma M, Justinova Z, Zanettini C, Panlilio LV, Mascia P, Fadda P, Fratta W, Makriyannis A, Vadivel SK, Gamaleddin I, Le Foll B, Goldberg SR (2012) The anandamide transport inhibitor AM404 reduces the rewarding effects of nicotine and nicotine-induced dopamine elevations in the nucleus accumbens shell in rats. Br J Pharmacol 165:2539–2548PubMedCentralPubMedGoogle Scholar
  195. Schilstrom B, Nomikos GG, Nisell M, Hertel P, Svensson TH (1998) N-methyl-D-aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens. Neuroscience 82:781–789PubMedGoogle Scholar
  196. Schilstrom B, Rawal N, Mameli-Engvall M, Nomikos GG, Svensson TH (2003) Dual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes. Int J Neuropsychopharmacol 6:1–11PubMedGoogle Scholar
  197. Schultz W (2004) Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology. Curr Opin Neurobiol 14:139–147PubMedGoogle Scholar
  198. Schultz W (2007) Multiple dopamine functions at different time courses. Annu Rev Neurosci 30:259–288PubMedGoogle Scholar
  199. Schultz W (2010) Dopamine signals for reward value and risk: basic and recent data. Behav Brain Functions 6:24Google Scholar
  200. Schultz W (2011) Potential vulnerabilities of neuronal reward, risk, and decision mechanisms to addictive drugs. Neuron 69:603–617PubMedGoogle Scholar
  201. Sellings LH, Clarke PB (2003) Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 23:6295–6303PubMedGoogle Scholar
  202. Sellings LH, McQuade LE, Clarke PB (2006) Evidence for multiple sites within rat ventral striatum mediating cocaine-conditioned place preference and locomotor activation. J Pharmacol Exp Ther 317:1178–1187PubMedGoogle Scholar
  203. Sellings LH, Baharnouri G, McQuade LE, Clarke PB (2008) Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens. Eur J Neurosci 28:342–352PubMedGoogle Scholar
  204. Sesack SR, Grace AA (2010) Cortico-Basal Ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27–47PubMedCentralPubMedGoogle Scholar
  205. Shoaib M, Stolerman IP (1999) Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats. Psychopharmacology 143:318–321PubMedGoogle Scholar
  206. Shoaib M, Benwell ME, Akbar MT, Stolerman IP, Balfour DJ (1994) Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists. Br J Pharmacol 111:1073–1080PubMedCentralPubMedGoogle Scholar
  207. Shoaib M, Schindler CW, Goldberg SR (1997) Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition. Psychopharmacology 129:35–43PubMedGoogle Scholar
  208. Shoaib M, Sidhpura N, Shafait S (2003) Investigating the actions of bupropion on dependence-related effects of nicotine in rats. Psychopharmacology 165:405–412PubMedGoogle Scholar
  209. Singer G, Wallace M (1984) Effects of 6-OHDA lesions in the nucleus accumbens on the acquisition of self injection of heroin under schedule and non schedule conditions in rats. Pharmacol Biochem Behav 20:807–809PubMedGoogle Scholar
  210. Singer G, Wallace M, Hall R (1982) Effects of dopaminergic nucleus accumbens lesions on the acquisition of schedule induced self injection of nicotine in the rat. Pharmacol Biochem Behav 17:579–581PubMedGoogle Scholar
  211. Spiller K, Xi ZX, Li X, Ashby CR Jr, Callahan PM, Tehim A, Gardner EL (2009) Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of alpha4beta2 nicotinic receptors in rats. Neuropharmacology 57:60–66PubMedCentralPubMedGoogle Scholar
  212. Stead LF, Lancaster T (2007) Interventions to reduce harm from continued tobacco use. Cochrane Database Syst Rev: CD005231Google Scholar
  213. Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, Lancaster T (2012) Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 11:CD000146Google Scholar
  214. Stefanik MT, Kupchik YM, Brown RM, Kalivas PW (2013) Optogenetic evidence that pallidal projections, not nigral projections, from the nucleus accumbens core are necessary for reinstating cocaine seeking. J Neurosci 33:13654–13662PubMedCentralPubMedGoogle Scholar
  215. Stuber GD, Roitman MF, Phillips PE, Carelli RM, Wightman RM (2005) Rapid dopamine signaling in the nucleus accumbens during contingent and noncontingent cocaine administration. Neuropsychopharmacology 30:853–863PubMedGoogle Scholar
  216. Suemaru K, Gomita Y, Furuno K, Araki Y (1993) Chronic nicotine treatment potentiates behavioral responses to dopaminergic drugs in rats. Pharmacol Biochem Behav 46:135–139PubMedGoogle Scholar
  217. Sutherland G, Russell MA, Stapleton J, Feyerabend C, Ferno O (1992) Nasal nicotine spray: a rapid nicotine delivery system. Psychopharmacology 108:512–518PubMedGoogle Scholar
  218. Taepavarapruk P, Floresco SB, Phillips AG (2000) Hyperlocomotion and increased dopamine efflux in the rat nucleus accumbens evoked by electrical stimulation of the ventral subiculum: role of ionotropic glutamate and dopamine D1 receptors. Psychopharmacology 151:242–251PubMedGoogle Scholar
  219. Tessari M, Pilla M, Andreoli M, Hutcheson DM, Heidbreder CA (2004) Antagonism at metabotropic glutamate 5 receptors inhibits nicotine- and cocaine-taking behaviours and prevents nicotine-triggered relapse to nicotine-seeking. Eur J Pharmacol 499:121–133PubMedGoogle Scholar
  220. Tronci V, Balfour DJ (2011) The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on the stimulation of dopamine release evoked by nicotine in the rat brain. Behav Brain Res 219:354–357PubMedGoogle Scholar
  221. Tronci V, Vronskaya S, Montgomery N, Mura D, Balfour DJ (2010) The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine. Psychopharmacology 211:33–42PubMedCentralPubMedGoogle Scholar
  222. Van Gucht D, Van den Bergh O, Beckers T, Vansteenwegen D (2010) Smoking behavior in context: where and when do people smoke? J Behav Ther Exp Psychiatry 41:172–177PubMedGoogle Scholar
  223. Vanderschuren LJ, Kalivas PW (2000) Alterations in dopam mergic and glutamatergic transmission in the induction and expression of behavioural sensitization: a critical review of preclinical studies. Psychopharmacology 151:99–120Google Scholar
  224. Vansickel AR, Eissenberg T (2013) Electronic cigarettes: effective nicotine delivery after acute administration. Nicotine Tob Res 15:267–270PubMedCentralPubMedGoogle Scholar
  225. Villegier AS, Lotfipour S, McQuown SC, Belluzzi JD, Leslie FM (2007) Tranylcypromine enhancement of nicotine self-administration. Neuropharmacology 52:1415–1425PubMedGoogle Scholar
  226. Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F (2011) Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci USA 108:15037–15042Google Scholar
  227. Warner C, Shoaib M (2005) How does bupropion work as a smoking cessation aid? Addict Biol 10:219–231PubMedGoogle Scholar
  228. Watkins SS, Stinus L, Koob GF, Markou A (2000) Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. J Pharmacol Exp Ther 292:1053–1064PubMedGoogle Scholar
  229. Wickham R, Solecki W, Rathbun L, McIntosh JM, Addy NA (2013) Ventral tegmental area alpha6beta2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core. Psychopharmacology 229:73–82PubMedCentralPubMedGoogle Scholar
  230. Willuhn I, Wanat MJ, Clark JJ, Phillips PE (2010) Dopamine signaling in the nucleus accumbens of animals self-administering drugs of abuse. Curr Top Behav Neurosci 3:29–71PubMedCentralPubMedGoogle Scholar
  231. Wing VC, Shoaib M (2008) Contextual stimuli modulate extinction and reinstatement in rodents self-administering intravenous nicotine. Psychopharmacology 200:357–365PubMedGoogle Scholar
  232. Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263PubMedGoogle Scholar
  233. Wise RA (1988a) The neurobiology of craving: implications for the understanding and treatment of addiction. J Abnorm Psychol 97:118–132PubMedGoogle Scholar
  234. Wise RA (1988b) Psychomotor stimulant properties of addictive drugs. Ann NY Acad Sci 537:228–234PubMedGoogle Scholar
  235. Wise RA (1996) Neurobiology of addiction. Curr Opin Neurobiol 6:243–251PubMedGoogle Scholar
  236. Wise RA, Bozarth MA (1985) Brain mechanisms of drug reward and euphoria. Psychiatr Med 3:445–460PubMedGoogle Scholar
  237. Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492PubMedGoogle Scholar
  238. Wouda JA, Riga D, De Vries W, Stegeman M, van Mourik Y, Schetters D, Schoffelmeer AN, Pattij T, De Vries TJ (2011) Varenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control. Psychopharmacology 216:267–277PubMedCentralPubMedGoogle Scholar
  239. Zahm DS, Brog JS (1992) On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience 50:751–767PubMedGoogle Scholar
  240. Zhang T, Zhang L, Liang Y, Siapas AG, Zhou FM, Dani JA (2009) Dopamine signaling differences in the nucleus accumbens and dorsal striatum exploited by nicotine. J Neurosci 29:4035–4043PubMedCentralPubMedGoogle Scholar
  241. Zhang L, Dong Y, Doyon WM, Dani JA (2012) Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in the nucleus accumbens. Biol Psychiatry 71:184–191PubMedCentralPubMedGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Medical Research Institute, Division of NeuroscienceNinewells Hospital and Medical SchoolDundeeScotland

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