Neuroscience Perspectives on Addiction: Overview

  • Anne Lingford-Hughes
  • Liam Nestor
Reference work entry


Substance addiction can be a chronic relapsing disorder. While different drugs of addiction have different primary molecular targets, it has been demonstrated that many share the common action of being able to increase dopamine within hard-wired reward circuitry. While this effect is widely conceived as a primary factor driving initial drug use, long-term adaptations within this hard-wired neural circuitry underlie the transition from drug use to drug dependence. Significantly, these neuroadaptations are responsible for triggering recurrent drug relapse in people recovering from addiction, even when following periods of long-term abstinence. While there is no animal model of addiction that can fully emulate the human condition, some animal models do permit the investigation of specific elements of drug addiction, particularly those involving the reward system and its role in drug-seeking behavior. Neuroimaging methods now also permit us to test hypotheses of addiction derived from such animal models, allowing the field of neuroscience to examine neural components of drug abuse and dependence in humans. These neuroimaging procedures permit neuroscientists to test hypotheses in humans at different stages of the addiction cycle, particularly with a view to developing better treatments.


Conditioned Stimulus Anterior Cingulate Cortex Ventral Tegmental Area Conditioned Place Preference Ventral Striatum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abi-Dargham, A., Krystal, J. H., Anjilvel, S., Scanley, B. E., Zoghbi, S., Baldwin, R. M., et al. (1998). Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil. The American Journal of Psychiatry, 155(11), 1550–1555.Google Scholar
  2. Aharonovich, E., Nunes, E., & Hasin, D. (2003). Cognitive impairment, retention and abstinence among cocaine abusers in cognitive-behavioral treatment. Drug and Alcohol Dependence, 71(2), 207–211.Google Scholar
  3. Aharonovich, E., Hasin, D. S., Brooks, A. C., Liu, X., Bisaga, A., & Nunes, E. V. (2006). Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug and Alcohol Dependence, 81(3), 313–322.Google Scholar
  4. Amara, S. G., & Kuhar, M. J. (1993). Neurotransmitter transporters: Recent progress. Annual Review of Neuroscience, 16, 73–93.Google Scholar
  5. Bardo, M. T., & Bevins, R. A. (2000). Conditioned place preference: What does it add to our preclinical understanding of drug reward? Psychopharmacology, 153(1), 31–43.Google Scholar
  6. Bechara, A. (2005). Decision making, impulse control and loss of willpower to resist drugs: A neurocognitive perspective. Nature Neuroscience, 8(11), 1458–1463.Google Scholar
  7. Bechara, A., Damasio, A. R., Damasio, H., & Anderson, S. W. (1994). Insensitivity to future consequences following damage to human prefrontal cortex. Cognition, 50(1–3), 7–15.Google Scholar
  8. Bechara, A., Dolan, S., Denburg, N., Hindes, A., Anderson, S. W., & Nathan, P. E. (2001). Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia, 39(4), 376–389.Google Scholar
  9. Beck, A., Schlagenhauf, F., Wustenberg, T., Hein, J., Kienast, T., Kahnt, T., et al. (2009). Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biological Psychiatry, 66(8), 734–742.Google Scholar
  10. Benowitz, N. L. (2008). Clinical pharmacology of nicotine: Implications for understanding, preventing, and treating tobacco addiction. Clinical Pharmacology and Therapeutics, 83(4), 531–541.Google Scholar
  11. Benowitz, N. L. (2009). Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annual Review of Pharmacology and Toxicology, 49, 57–71.Google Scholar
  12. Berridge, K. C. (2009). Wanting and liking: Observations from the neuroscience and psychology laboratory. Inquiry (Oslo), 52(4), 378.Google Scholar
  13. Berridge, K. C., & Robinson, T. E. (1998). What is the role of dopamine in reward: Hedonic impact, reward learning, or incentive salience? Brain Research. Brain Research Reviews, 28(3), 309–369.Google Scholar
  14. Berridge, K. C., Robinson, T. E., & Aldridge, J. W. (2009). Dissecting components of reward: ‘Liking’, ‘wanting’, and learning. Current Opinion in Pharmacology, 9(1), 65–73.Google Scholar
  15. Bickel, W., & Marsch, L. (2001). Toward a behavioral economic understanding of drug dependence: Delay discounting processes. Addiction, 96(1), 73–86.Google Scholar
  16. Bickel, W. K., Miller, M. L., Yi, R., Kowal, B. P., Lindquist, D. M., & Pitcock, J. A. (2007). Behavioral and neuroeconomics of drug addiction: Competing neural systems and temporal discounting processes. Drug and Alcohol Dependence, 90(Suppl 1), S85–S91.Google Scholar
  17. Bjork, J. M., Hommer, D. W., Grant, S. J., & Danube, C. (2004). Impulsivity in abstinent alcohol-dependent patients: Relation to control subjects and type 1-/type 2-like traits. Alcohol, 34(2–3), 133–150.Google Scholar
  18. Bjork, J. M., Smith, A. R., & Hommer, D. W. (2008). Striatal sensitivity to reward deliveries and omissions in substance dependent patients. NeuroImage, 42(4), 1609–1621.Google Scholar
  19. Blum, K., Braverman, E. R., Holder, J. M., Lubar, J. F., Monastra, V. J., Miller, D., et al. (2000). Reward deficiency syndrome: A biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. Journal of Psychoactive Drugs, 32(Suppl i–iv), 1–112.Google Scholar
  20. Bolla, K. I., Eldreth, D. A., London, E. D., Kiehl, K. A., Mouratidis, M., Contoreggi, C., et al. (2003). Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. NeuroImage, 19, 1085–1094.Google Scholar
  21. Bolla, K. I., Eldreth, D. A., Matochik, J. A., & Cadet, J. L. (2005). Neural substrates of faulty decision-making in abstinent marijuana users. NeuroImage, 26(2), 480–492.Google Scholar
  22. Bossong, M. G., van Berckel, B. N., Boellaard, R., Zuurman, L., Schuit, R. C., Windhorst, A. D., et al. (2009). Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology, 34(3), 759–766.Google Scholar
  23. Brody, A. L., Olmstead, R. E., London, E. D., Farahi, J., Meyer, J. H., Grossman, P., et al. (2004). Smoking-induced ventral striatum dopamine release. The American Journal of Psychiatry, 161(7), 1211–1218.Google Scholar
  24. Brody, A. L., Mandelkern, M. A., London, E. D., Olmstead, R. E., Farahi, J., Scheibal, D., et al. (2006). Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Archives of General Psychiatry, 63(8), 907–915.Google Scholar
  25. Bruijnzeel, A. W. (2009). Kappa-Opioid receptor signaling and brain reward function. Brain Research Reviews, 62(1), 127–146.Google Scholar
  26. Burger, L. Y., & Martin-Iverson, M. T. (1994). Increased occupation of D1 and D2 dopamine receptors accompanies cocaine-induced behavioral sensitization. Brain Research, 639(2), 228–232.Google Scholar
  27. Cami, J., & Farre, M. (2003). Drug addiction. The New England Journal of Medicine, 349(10), 975–986.Google Scholar
  28. Carter, C., Braver, T., Barch, D., Botvinick, M., Noll, D., & Cohen, J. D. (1998). Anterior cingulate cortex, error detection, and the online monitoring of performance. Science, 280(5364), 747–749.Google Scholar
  29. Curran, H. V., Brignell, C., Fletcher, S., Middleton, P., & Henry, J. (2002). Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology, 164(1), 61–70.Google Scholar
  30. D’Souza, D. C., Braley, G., Blaise, R., Vendetti, M., Oliver, S., Pittman, B., et al. (2008). Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology, 198(4), 587–603.Google Scholar
  31. Dagher, A., Bleicher, C., Aston, J. A., Gunn, R. N., Clarke, P. B., & Cumming, P. (2001). Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers. Synapse, 42(1), 48–53.Google Scholar
  32. Daglish, M. R., Weinstein, A., Malizia, A. L., Wilson, S., Melichar, J. K., Britten, S., et al. (2001). Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects. The American Journal of Psychiatry, 158(10), 1680–1686.Google Scholar
  33. Daglish, M. R. C., Williams, T., Wilson, S. J., Taylor, L. G., Brooks, D. J., Myles, J. S., Grasby, P. G., Lingford-Hughes, A. R., & Nutt, D. J. (2008). No measurable dopamine response to heroin in the brains of human addicts. The British Journal of Psychiatry, 193(1), 65–72.Google Scholar
  34. Degoulet, M. F., Rostain, J. C., David, H. N., & Abraini, J. H. (2009). Repeated administration of amphetamine induces a shift of the prefrontal cortex and basolateral amygdala motor function. The International Journal of Neuropsychopharmacology, 12(7), 965–974.Google Scholar
  35. Ding, Y. S., Gatley, S. J., Thanos, P. K., Shea, C., Garza, V., Xu, Y., et al. (2004). Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration. Synapse, 53(3), 168–175.Google Scholar
  36. Drenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., et al. (2010). Cholinergic modulation of locomotion and striatal dopamine release is mediated by alpha6alpha4* nicotinic acetylcholine receptors. Journal of Neuroscience, 30(29), 9877–9889.Google Scholar
  37. Ernst, M., Bolla, K., Mouratidis, M., Contoreggi, C., Matochik, J. A., Kurian, V., et al. (2002). Decision-making in a risk-taking task: A PET study. Neuropsychopharmacology, 26(5), 682–691.Google Scholar
  38. Everitt, B. J., & Robbins, T. W. (2005). Neural systems of reinforcement for drug addiction: From actions to habits to compulsion. Nature Neuroscience, 8(11), 1481–1489.Google Scholar
  39. Feltenstein, M. W., & See, R. E. (2008). The neurocircuitry of addiction: An overview. British Journal of Pharmacology, 154(2), 261–274.Google Scholar
  40. Fergusson, D. M., Horwood, L. J., & Ridder, E. M. (2007). Conduct and attentional problems in childhood and adolescence and later substance use, abuse and dependence: Results of a 25-year longitudinal study. Drug and Alcohol Dependence, 88(Suppl 1), S14–S26.Google Scholar
  41. Forman, S. D., Dougherty, G. G., Casey, B. J., Siegle, G. J., Braver, T. S., Barch, D. M., et al. (2004). Opiate addicts lack error-dependent activation of rostral anterior cingulate. Biological Psychiatry, 55(5), 531–537.Google Scholar
  42. Franklin, T., Wang, Z., Suh, J. J., Hazan, R., Cruz, J., Li, Y., et al. (2011). Effects of varenicline on smoking cue-triggered neural and craving responses. Archives of General Psychiatry, 68(5), 516–526.Google Scholar
  43. Garavan, H., & Stout, J. C. (2005). Neurocognitive insights into substance abuse. Trends in Cognitive Science, 9(4), 195–201.Google Scholar
  44. Garavan, H., Ross, T. J., & Stein, E. A. (1999). Right hemispheric dominance of inhibitory control: An event-related functional MRI study. Proceedings of the National Academy of Sciences of the United States of America, 96(14), 8301–8306.Google Scholar
  45. Garavan, H., Ross, T. J., Murphy, K., Roche, R. A., & Stein, E. A. (2002). Dissociable executive functions in the dynamic control of behavior: Inhibition, error detection, and correction. NeuroImage, 17(4), 1820–1829.Google Scholar
  46. Garavan, H., Kaufman, J. N., & Hester, R. (2008). Acute effects of cocaine on the neurobiology of cognitive control. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 363(1507), 3267–3276.Google Scholar
  47. Ghitza, U. E., Preston, K. L., Epstein, D. H., Kuwabara, H., Endres, C. J., Bencherif, B., et al. (2010). Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients. Biological Psychiatry, 68(8), 697–703.Google Scholar
  48. Goldstein, R. Z., & Volkow, N. D. (2002). Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex. The American Journal of Psychiatry, 159, 1642–1652.Google Scholar
  49. Goldstein, R. Z., Leskovjan, A. C., Hoff, A. L., Hitzemann, R., Bashan, F., Khalsa, S. S., et al. (2004). Severity of neuropsychological impairment in cocaine and alcohol addiction: Association with metabolism in the prefrontal cortex. Neuropsychologia, 42(11), 1447–1458.Google Scholar
  50. Goldstein, R. Z., Tomasi, D., Alia-Klein, N., Cottone, L. A., Zhang, L., Telang, F., et al. (2007a). Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers. Drug and Alcohol Dependence, 87(2–3), 233–240.Google Scholar
  51. Goldstein, R. Z., Tomasi, D., Rajaram, S., Cottone, L. A., Zhang, L., Maloney, T., et al. (2007b). Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction. Neuroscience, 144(4), 1153–1159.Google Scholar
  52. Goldstein, R. Z., Woicik, P. A., Maloney, T., Tomasi, D., Alia-Klein, N., Shan, J., et al. (2010). Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task. Proceedings of the National Academy of Sciences of the United States of America, 107(38), 16667–16672.Google Scholar
  53. Gonzales, D., Rennard, S. I., Nides, M., Oncken, C., Azoulay, S., Billing, C. B., et al. (2006). Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA: The Journal of the American Medical Association, 296(1), 47–55.Google Scholar
  54. Gorelick, D. A., Kim, Y. K., Bencherif, B., Boyd, S. J., Nelson, R., Copersino, M., et al. (2005). Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving. Biological Psychiatry, 57(12), 1573–1582.Google Scholar
  55. Grady, S. R., Salminen, O., McIntosh, J. M., Marks, M. J., & Collins, A. C. (2010). Mouse striatal dopamine nerve terminals express alpha4alpha5beta2 and two stoichiometric forms of alpha4beta2*-nicotinic acetylcholine receptors. Journal of Molecular Neuroscience, 40(1–2), 91–95.Google Scholar
  56. Gray, R., Rajan, A. S., Radcliffe, K. A., Yakehiro, M., & Dani, J. A. (1996). Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature, 383(6602), 713–716.Google Scholar
  57. Heidbreder, C. (2011). Advances in animal models of drug addiction. Current Topics in Behavioral Neurosciences, 7, 213–250.Google Scholar
  58. Heil, S. H., Johnson, M. W., Higgins, S. T., & Bickel, W. K. (2006). Delay discounting in currently using and currently abstinent cocaine-dependent outpatients and non-drug-using matched controls. Addictive Behaviors, 31(7), 1290–1294.Google Scholar
  59. Heimer, L., & Van Hoesen, G. W. (2006). The limbic lobe and its output channels: Implications for emotional functions and adaptive behavior. Neuroscience and Biobehavioral Reviews, 30(2), 126–147.Google Scholar
  60. Heinz, A., Siessmeier, T., Wrase, J., Hermann, D., Klein, S., Grusser, S. M., et al. (2004). Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. The American Journal of Psychiatry, 161(10), 1783–1789.Google Scholar
  61. Heinz, A., Reimold, M., Wrase, J., Hermann, D., Croissant, B., Mundle, G., et al. (2005). Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: A positron emission tomography study using carbon 11-labeled carfentanil. Archives of General Psychiatry, 62(1), 57–64.Google Scholar
  62. Heishman, S. J., Schuh, K. J., Schuster, C. R., Henningfield, J. E., & Goldberg, S. R. (2000). Reinforcing and subjective effects of morphine in human opioid abusers: Effect of dose and alternative reinforcer. Psychopharmacology, 148(3), 272–280.Google Scholar
  63. Herkenham, M., Lynn, A. B., Johnson, M. R., Melvin, L. S., de Costa, B. R., & Rice, K. C. (1991). Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. Journal of Neuroscience, 11(2), 563–583.Google Scholar
  64. Hester, R., & Garavan, H. (2004). Executive dysfunction in cocaine addiction: Evidence for discordant frontal, cingulate, and cerebellar activity. Journal of Neuroscience, 24(49), 11017–11022.Google Scholar
  65. Hester, R., Nestor, L., & Garavan, H. (2009). Impaired error awareness and anterior cingulate cortex hypoactivity in chronic cannabis users. Neuropsychopharmacology, 34(11), 2450–2458.Google Scholar
  66. Hill, J. L., & Zacny, J. P. (2000). Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers. Psychopharmacology, 152(1), 31–39.Google Scholar
  67. Hoffman, W. F., Schwartz, D. L., Huckans, M. S., McFarland, B. H., Meiri, G., Stevens, A. A., et al. (2008). Cortical activation during delay discounting in abstinent methamphetamine dependent individuals. Psychopharmacology, 201(2), 183–193.Google Scholar
  68. Howell, L. L., & Kimmel, H. L. (2008). Monoamine transporters and psychostimulant addiction. Biochemical Pharmacology, 75(1), 196–217.Google Scholar
  69. Huestis, M. A., Boyd, S. J., Heishman, S. J., Preston, K. L., Bonnet, D. L., Fur, G., et al. (2007). Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology, 194(4), 505–515.Google Scholar
  70. Hunault, C. C., Mensinga, T. T., de Vries, I., Kelholt-Dijkman, H. H., Hoek, J., Kruidenier, M., et al. (2008). Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC. Psychopharmacology, 201(2), 171–181.Google Scholar
  71. Janes, A. C., Pizzagalli, D. A., Richardt, S., deB Frederick, B., Chuzi, S., Pachas, G., et al. (2010). Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biological Psychiatry, 67(8), 722–729.Google Scholar
  72. Jia, Z., Worhunsky, P. D., Carroll, K. M., Rounsaville, B. J., Stevens, M. C., Pearlson, G. D., et al. (2011). An initial study of neural responses to monetary incentives as related to treatment outcome in cocaine dependence. Biological Psychiatry, 70(6), 553–560.Google Scholar
  73. Jorenby, D. E., Hays, J. T., Rigotti, N. A., Azoulay, S., Watsky, E. J., Williams, K. E., et al. (2006). Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA: The Journal of the American Medical Association, 296(1), 56–63.Google Scholar
  74. Kaufman, J. N., Ross, T. J., Stein, E. A., & Garavan, H. (2003). Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging. Journal of Neuroscience, 23(21), 7839–7843.Google Scholar
  75. Klink, R., de Kerchove d’Exaerde, A., Zoli, M., & Changeux, J. P. (2001). Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. Journal of Neuroscience, 21(5), 1452–1463.Google Scholar
  76. Knutson, B., Adams, C. M., Fong, G. W., & Hommer, D. (2001). Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Journal of Neuroscience, 21(16), RC159.Google Scholar
  77. Koob, G. F. (2004). A role for GABA mechanisms in the motivational effects of alcohol. Biochemical Pharmacology, 68(8), 1515–1525.Google Scholar
  78. Koob, G. F., & Le Moal, M. (1997). Drug abuse: Hedonic homeostatic dysregulation. Science, 278(5335), 52–58.Google Scholar
  79. Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology, 35(1), 217–238.Google Scholar
  80. Koob, G. F., Ahmed, S. H., Boutrel, B., Chen, S. A., Kenny, P. J., Markou, A., et al. (2004). Neurobiological mechanisms in the transition from drug use to drug dependence. Neuroscience and Biobehavioral Reviews, 27(8), 739–749.Google Scholar
  81. Kosowski, A. R., & Liljequist, S. (2005). Behavioural sensitization to nicotine precedes the onset of nicotine-conditioned locomotor stimulation. Behavioural Brain Research, 156(1), 11–17.Google Scholar
  82. Kruzich, P. J., & See, R. E. (2001). Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior. Journal of Neuroscience, 21(14), RC155.Google Scholar
  83. Kruzich, P. J., Congleton, K. M., & See, R. E. (2001). Conditioned reinstatement of drug-seeking behavior with a discrete compound stimulus classically conditioned with intravenous cocaine. Behavioral Neuroscience, 115(5), 1086–1092.Google Scholar
  84. Kubler, A., Murphy, K., & Garavan, H. (2005). Cocaine dependence and attention switching within and between verbal and visuospatial working memory. European Journal of Neuroscience, 21(7), 1984–1992.Google Scholar
  85. Kuhar, M. J., Ritz, M. C., & Boja, J. W. (1991). The dopamine hypothesis of the reinforcing properties of cocaine. Trends in Neurosciences, 14(7), 299–302.Google Scholar
  86. Langleben, D. D., Ruparel, K., Elman, I., Busch-Winokur, S., Pratiwadi, R., Loughead, J., et al. (2008). Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. The American Journal of Psychiatry, 165(3), 390–394.Google Scholar
  87. Lee, B., London, E. D., Poldrack, R. A., Farahi, J., Nacca, A., Monterosso, J. R., et al. (2009). Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. Journal of Neuroscience, 29(47), 14734–14740.Google Scholar
  88. Leroy, C., Karila, L., Martinot, J. L., Lukasiewicz, M., Duchesnay, E., Comtat, C., et al. (2011). Striatal and extrastriatal dopamine transporter in cannabis and tobacco addiction: A high-resolution PET study. Addiction Biology, 17(6):981–90.Google Scholar
  89. Lingford-Hughes, A. R., Acton, P. D., Gacinovic, S., Suckling, J., Busatto, G. F., Boddington, S. J. A., Bullmore, E., Woodruff, P. W., Costa, D. C., Pilowsky, L. S., Ell, P. J., Marshall, E. J., & Kerwin, R. W. (1998). Reduced levels of the GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy. The British Journal of Psychiatry, 173, 116–122.Google Scholar
  90. Lingford-Hughes, A. R., Wilson, S. J., Cunningham, V. J., Feeney, A., Stevenson, B., Brooks, D. J., & Nutt, D. J. (2005). GABA-benzodiazepine receptor function in alcohol dependence: A combined 11C-flumazenil PET and pharmacodynamic study. Psychopharmacology, 180, 595–606.Google Scholar
  91. Lingford-Hughes, A. R., Watson, B., Kalk, N., & Reid, A. (2010). Neuropharmacology of addiction and how it informs treatment. British Medical Bulletin, 96, 93–110.Google Scholar
  92. Lingford-Hughes, A., Welch, S., Peters, L., Nutt, D. on behalf of expert group. (2012a). Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: Recommendations from BAP. Journal of Psychopharmacology, 26(7), 899–952.Google Scholar
  93. Lingford-Hughes, A. R., Reid, A. G., Myers, J., Feeney, A., Hammers, A., Taylor, L. G., Rosso, L., Turkheimer, F., Brooks, D. J., Grasby, P., & Nutt, D. J. (2012b). A [11C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced a5 benzodiazepine receptors in limbic regions. Journal of Psychopharmacology, 26(2), 273–281.Google Scholar
  94. Lippiello, P., Letchworth, S. R., Gatto, G. J., Traina, V. M., & Bencherif, M. (2006). Ispronicline: A novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties. Journal of Molecular Neuroscience, 30(1–2), 19–20.Google Scholar
  95. Luo, S., Ainslie, G., Giragosian, L., & Monterosso, J. R. (2011). Striatal hyposensitivity to delayed rewards among cigarette smokers. Drug and Alcohol Dependence, 116(1–3), 18–23.Google Scholar
  96. Mameli-Engvall, M., Evrard, A., Pons, S., Maskos, U., Svensson, T. H., Changeux, J. P., et al. (2006). Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron, 50(6), 911–921.Google Scholar
  97. Mansvelder, H. D., & McGehee, D. S. (2002). Cellular and synaptic mechanisms of nicotine addiction. Journal of Neurobiology, 53(4), 606–617.Google Scholar
  98. Martinez, D., Gil, R., Slifstein, M., Hwang, D. R., Huang, Y., Perez, A., et al. (2005). Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biological Psychiatry, 58(10), 779–786.Google Scholar
  99. Martinez, D., Narendran, R., Foltin, R. W., Slifstein, M., Hwang, D. R., Broft, A., et al. (2007). Amphetamine-induced dopamine release: Markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. The American Journal of Psychiatry, 164(4), 622–629.Google Scholar
  100. Martinez, D., Greene, K., Broft, A., Kumar, D., Liu, F., Narendran, R., et al. (2009). Lower level of endogenous dopamine in patients with cocaine dependence: Findings from PET imaging of D(2)/D(3) receptors following acute dopamine depletion. The American Journal of Psychiatry, 166(10), 1170–1177.Google Scholar
  101. Martinez, D., Saccone, P. A., Liu, F., Slifstein, M., Orlowska, D., Grassetti, A., et al. (2011). Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: Commonalities and differences with other types of addiction. Biological Psychiatry, 71(3):192–8.Google Scholar
  102. Masse, L. C., & Tremblay, R. E. (1997). Behavior of boys in kindergarten and the onset of substance use during adolescence. Archives of General Psychiatry, 54(1), 62–68.Google Scholar
  103. Mathers, C. D., & Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine, 3(11), e442.Google Scholar
  104. Matthews, S. C., Simmons, A. N., Lane, S. D., & Paulus, M. P. (2004). Selective activation of the nucleus accumbens during risk-taking decision making. Neuroreport, 15(13), 2123–2127.Google Scholar
  105. McClernon, F. J., Hiott, F. B., Liu, J., Salley, A. N., Behm, F. M., & Rose, J. E. (2007). Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: Results of a preliminary functional magnetic resonance imaging study. Addiction Biology, 12(3–4), 503–512.Google Scholar
  106. Mei, W., Zhang, J. X., & Xiao, Z. (2010). Acute effects of sublingual buprenorphine on brain responses to heroin-related cues in early-abstinent heroin addicts: An uncontrolled trial. Neuroscience, 170(3), 808–815.Google Scholar
  107. Moeller, F. G., Steinberg, J. L., Schmitz, J. M., Ma, L., Liu, S., Kjome, K. L., et al. (2010). Working memory fMRI activation in cocaine-dependent subjects: Association with treatment response. Psychiatry Research, 181(3), 174–182.Google Scholar
  108. Monterosso, J. R., Ainslie, G., Xu, J., Cordova, X., Domier, C. P., & London, E. D. (2007). Frontoparietal cortical activity of methamphetamine-dependent and comparison subjects performing a delay discounting task. Human Brain Mapping, 28(5), 383–393.Google Scholar
  109. Muraven, M. (2010). Practicing self-control lowers the risk of smoking lapse. Psychology of Addictive Behaviors, 24(3), 446–452.Google Scholar
  110. Myers, M. G., Brown, S. A., & Mott, M. A. (1995). Preadolescent conduct disorder behaviors predict relapse and progression of addiction for adolescent alcohol and drug abusers. Alcoholism, Clinical and Experimental Research, 19(6), 1528–1536.Google Scholar
  111. Myrick, H., Anton, R. F., Li, X., Henderson, S., Randall, P. K., & Voronin, K. (2008). Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. Archives of General Psychiatry, 65(4), 466–475.Google Scholar
  112. Myrick, H., Li, X., Randall, P. K., Henderson, S., Voronin, K., & Anton, R. F. (2010). The effect of aripiprazole on cue-induced brain activation and drinking parameters in alcoholics. Journal of Clinical Psychopharmacology, 30(4), 365–372.Google Scholar
  113. Naqvi, N. H., & Bechara, A. (2008). The hidden island of addiction: The insula. Trends in Neurosciences, 32(1):56–67.Google Scholar
  114. Nestor, L., Hester, R., & Garavan, H. (2010). Increased ventral striatal BOLD activity during non-drug reward anticipation in cannabis users. NeuroImage, 49(1), 1133–1143.Google Scholar
  115. Nestor, L., McCabe, E., Jones, J., Clancy, L., & Garavan, H. (2011a). Differences in “bottom-up” and “top-down” neural activity in current and former cigarette smokers: Evidence for neural substrates which may promote nicotine abstinence through increased cognitive control. NeuroImage, 56(4), 2258–2275.Google Scholar
  116. Nestor, L. J., Ghahremani, D. G., Monterosso, J., & London, E. D. (2011b). Prefrontal hypoactivation during cognitive control in early abstinent methamphetamine-dependent subjects. Psychiatry Research, 194(3), 287–295.Google Scholar
  117. Nutt, D. J., & Lingford-Hughes, A. R. (2008). Addiction: The clinical interface. British Journal of Pharmacology, 154(2), 397–405.Google Scholar
  118. Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47(6), 419–427.Google Scholar
  119. Pastor, V., Andres, M. E., & Bernabeu, R. O. (2012). The effect of previous exposure to nicotine on nicotine place preference. Psychopharmacology (Berlin), 226(3):551–60.Google Scholar
  120. Patterson, F., Jepson, C., Strasser, A. A., Loughead, J., Perkins, K. A., Gur, R. C., et al. (2009). Varenicline improves mood and cognition during smoking abstinence. Biological Psychiatry, 65(2), 144–149.Google Scholar
  121. Paulus, M. P., Hozack, N., Frank, L., Brown, G. G., & Schuckit, M. A. (2003). Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation. Biological Psychiatry, 53(1), 65–74.Google Scholar
  122. Paulus, M. P., Tapert, S. F., & Schuckit, M. A. (2005). Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Archives of General Psychiatry, 62(7), 761–768.Google Scholar
  123. Peters, J., Bromberg, U., Schneider, S., Brassen, S., Menz, M., Banaschewski, T., et al. (2011). Lower ventral striatal activation during reward anticipation in adolescent smokers. The American Journal of Psychiatry, 168(5), 540–549.Google Scholar
  124. Peto, R., Lopez, A. D., Boreham, J., Thun, M., Heath, C., Jr., & Doll, R. (1996). Mortality from smoking worldwide. British Medical Bulletin, 52(1), 12–21.Google Scholar
  125. Reynolds, B., & Fields, S. (2011). Delay discounting by adolescents experimenting with cigarette smoking. Addiction, 107(2):417–24.Google Scholar
  126. Ridderinkhof, K. R., Ullsperger, M., Crone, E. A., & Nieuwenhuis, S. (2004a). The role of the medial frontal cortex in cognitive control. Science, 306(5695), 443–447.Google Scholar
  127. Ridderinkhof, K. R., van den Wildenberg, W. P., Segalowitz, S. J., & Carter, C. S. (2004b). Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. Brain and Cognition, 56(2), 129–140.Google Scholar
  128. Robinson, T. E., & Berridge, K. C. (2000). The psychology and neurobiology of addiction: An incentive-sensitization view. Addiction, 95(Suppl 2), S91–S117.Google Scholar
  129. Robles, E., Huang, B. E., Simpson, P. M., & McMillan, D. E. (2011). Delay discounting, impulsiveness, and addiction severity in opioid-dependent patients. Journal of Substance Abuse Treatment, 41(4), 354–362.Google Scholar
  130. Rudnick, G., & Clark, J. (1993). From synapse to vesicle: The reuptake and storage of biogenic amine neurotransmitters. Biochimica et Biophysica Acta, 1144(3), 249–263.Google Scholar
  131. Schoenmakers, T. M., de Bruin, M., Lux, I. F., Goertz, A. G., Van Kerkhof, D. H., & Wiers, R. W. (2010). Clinical effectiveness of attentional bias modification training in abstinent alcoholic patients. Drug and Alcohol Dependence, 109(1–3), 30–36.Google Scholar
  132. Schott, B. H., Minuzzi, L., Krebs, R. M., Elmenhorst, D., Lang, M., Winz, O. H., et al. (2008). Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. Journal of Neuroscience, 28(52), 14311–14319.Google Scholar
  133. Sevy, S., Smith, G. S., Ma, Y., Dhawan, V., Chaly, T., Kingsley, P. B., et al. (2008). Cerebral glucose metabolism and D(2)/D (3) receptor availability in young adults with cannabis dependence measured with positron emission tomography. Psychopharmacology, 197(4), 549–556.Google Scholar
  134. Shaham, Y., Shalev, U., Lu, L., De Wit, H., & Stewart, J. (2003). The reinstatement model of drug relapse: History, methodology and major findings. Psychopharmacology, 168(1–2), 3–20.Google Scholar
  135. Shoptaw, S., Heinzerling, K. G., Rotheram-Fuller, E., Kao, U. H., Wang, P. C., Bholat, M. A., et al. (2008). Bupropion hydrochloride versus placebo, in combination with cognitive behavioral therapy, for the treatment of cocaine abuse/dependence. Journal of Addictive Diseases, 27(1), 13–23.Google Scholar
  136. Sieghart, W. (2006). Structure, pharmacology, and function of GABAA receptor subtypes. Advances in Pharmacology, 54, 231–263.Google Scholar
  137. Sinha, R., & Li, C. S. (2007). Imaging stress- and cue-induced drug and alcohol craving: Association with relapse and clinical implications. Drug and Alcohol Review, 26(1), 25–31.Google Scholar
  138. Solomon, R. L., & Corbit, J. D. (1974). An opponent-process theory of motivation. I. Temporal dynamics of affect. Psychological Review, 81(2), 119–145.Google Scholar
  139. Sora, I., Li, B., Fumushima, S., Fukui, A., Arime, Y., Kasahara, Y., et al. (2009). Monoamine transporter as a target molecule for psychostimulants. International Review of Neurobiology, 85, 29–33.Google Scholar
  140. Sticht, M., Mitsubata, J., Tucci, M., & Leri, F. (2010). Reacquisition of heroin and cocaine place preference involves a memory consolidation process sensitive to systemic and intra-ventral tegmental area naloxone. Neurobiology of Learning and Memory, 93(2), 248–260.Google Scholar
  141. Stokes, P. R., Mehta, M. A., Curran, H. V., Breen, G., & Grasby, P. M. (2009). Can recreational doses of THC produce significant dopamine release in the human striatum? NeuroImage, 48(1), 186–190.Google Scholar
  142. Stokes, P. R. A., Egerton, A., Watson, B., Reid, A., Lappin, J., Nutt, D., & Lingford-Hughes, A. (2012). History of cannabis use is not associated with alterations in striatal dopamine D2/D3 receptor availability. Journal of Psychopharmacology, 26(1), 144–149.Google Scholar
  143. Sullivan, J. M., Risacher, S. L., Normandin, M. D., Yoder, K. K., Froehlich, J. C., & Morris, E. D. (2011). Imaging of alcohol-induced dopamine release in rats: Preliminary findings with [(11) C]raclopride PET. Synapse, 65(9), 929–937.Google Scholar
  144. Tang, A., George, M. A., Randall, J. A., & Gonzales, R. A. (2003). Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice. Alcoholism, Clinical and Experimental Research, 27(7), 1083–1089.Google Scholar
  145. Thorn, D. A., Winter, J. C., & Li, J. X. (2012). Agmatine attenuates methamphetamine-induced conditioned place preference in rats. European Journal of Pharmacology, 680(1–3), 69–72.Google Scholar
  146. Tomasi, D., Goldstein, R. Z., Telang, F., Maloney, T., Alia-Klein, N., Caparelli, E. C., et al. (2007). Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence. Brain Research, 1171, 83–92.Google Scholar
  147. Tsou, K., Brown, S., Sanudo-Pena, M. C., Mackie, K., & Walker, J. M. (1998). Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience, 83(2), 393–411.Google Scholar
  148. Ullsperger, M., & von Cramon, D. Y. (2001). Subprocesses of performance monitoring: A dissociation of error processing and response competition revealed by event-related fMRI and ERPs. NeuroImage, 14(6), 1387–1401.Google Scholar
  149. van Hell, H. H., Vink, M., Ossewaarde, L., Jager, G., Kahn, R. S., & Ramsey, N. F. (2010). Chronic effects of cannabis use on the human reward system: An fMRI study. European Neuropsychopharmacology, 20(3), 153–163.Google Scholar
  150. Vanderschuren, L. J., & Kalivas, P. W. (2000). Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: A critical review of preclinical studies. Psychopharmacology, 151(2–3), 99–120.Google Scholar
  151. Verdejo-Garcia, A., & Bechara, A. (2009). A somatic marker theory of addiction. Neuropharmacology, 56(Suppl 1), 48–62.Google Scholar
  152. Verney, S. P., Brown, G. G., Frank, L., & Paulus, M. P. (2003). Error-rate-related caudate and parietal cortex activation during decision making. Neuroreport, 14(7), 923–928.Google Scholar
  153. Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Hitzemann, R., Ding, Y. S., et al. (1996). Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcoholism, Clinical and Experimental Research, 20(9), 1594–1598.Google Scholar
  154. Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Gatley, S. J., Hitzemann, R., et al. (1997). Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature, 386(6627), 830–833.Google Scholar
  155. Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Gatley, S. J., Wong, C., et al. (1999). Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors. Journal of Pharmacology and Experimental Therapeutics, 291(1), 409–415.Google Scholar
  156. Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Ding, Y. S., Sedler, M., et al. (2001). Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex. The American Journal of Psychiatry, 158(12), 2015–2021.Google Scholar
  157. Volkow, N., Fowler, J., Wang, G., & Goldstein, R. (2002a). Role of dopamine, the frontal cortex and memory circuits in drug addiction: Insight from imaging studies. Neurobiology of Learning and Memory, 78(3), 610–624.Google Scholar
  158. Volkow, N. D., Wang, G. J., Maynard, L., Fowler, J. S., Jayne, B., Telang, F., et al. (2002b). Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: A preliminary study. Psychiatry Research, 116(3), 163–172.Google Scholar
  159. Volkow, N. D., Fowler, J. S., Wang, G. J., & Swanson, J. M. (2004). Dopamine in drug abuse and addiction: Results from imaging studies and treatment implications. Molecular Psychiatry, 9(6), 557–569.Google Scholar
  160. Volkow, N. D., Wang, G. J., Begleiter, H., Porjesz, B., Fowler, J. S., Telang, F., et al. (2006a). High levels of dopamine D2 receptors in unaffected members of alcoholic families: Possible protective factors. Archives of General Psychiatry, 63(9), 999–1008.Google Scholar
  161. Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Childress, A. R., et al. (2006b). Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction. Journal of Neuroscience, 26(24), 6583–6588.Google Scholar
  162. Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Jayne, M., et al. (2007). Profound decreases in dopamine release in striatum in detoxified alcoholics: Possible orbitofrontal involvement. Journal of Neuroscience, 27(46), 12700–12706.Google Scholar
  163. Vollstadt-Klein, S., Wichert, S., Rabinstein, J., Buhler, M., Klein, O., Ende, G., et al. (2010). Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum. Addiction, 105(10), 1741–1749.Google Scholar
  164. Weerts, E. M., Wand, G. S., Kuwabara, H., Munro, C. A., Dannals, R. F., Hilton, J., et al. (2011). Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects. Alcoholism, Clinical and Experimental Research, 35(12), 2162–2173.Google Scholar
  165. Weiss, F., Maldonado-Vlaar, C. S., Parsons, L. H., Kerr, T. M., Smith, D. L., & Ben-Shahar, O. (2000). Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens. Proceedings of the National Academy of Sciences of the United States of America, 97(8), 4321–4326.Google Scholar
  166. Wexler, B. E., Gottschalk, C. H., Fulbright, R. K., Prohovnik, I., Lacadie, C. M., Rounsaville, B. J., et al. (2001). Functional magnetic resonance imaging of cocaine craving. The American Journal of Psychiatry, 158(1), 86–95.Google Scholar
  167. Williams, T. M., Daglish, M. R. C., Lingford-Hughes, A. R., Taylor, L. G., Hammers, A., Brooks, D. J., Grasby, P. G., Myles, J. S., & Nutt, D. J. (2007). Increased availability of opioid receptors in early abstinence from opioid dependence: A [11C]diprenorphine PET study. The British Journal of Psychiatry, 191(1), 63–69.Google Scholar
  168. Williams, T. M., Davies, S. J., Taylor, L. G., Daglish, M. R., Hammers, A., Brooks, D. J., Nutt, D. J., & Lingford-Hughes, A. (2009). Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: An [(11)C]diprenorphine PET study. European Neuropsychopharmacology, 19(10), 740–748.Google Scholar
  169. Wise, R. A. (1996). Neurobiology of addiction. Current Opinion in Neurobiology, 6(2), 243–251.Google Scholar
  170. Wise, R. A. (2002). Brain reward circuitry: Insights from unsensed incentives. Neuron, 36(2), 229–240.Google Scholar
  171. Wise, R. A. (2005). Forebrain substrates of reward and motivation. The Journal of Comparative Neurology, 493(1), 115–121.Google Scholar
  172. Wooltorton, J. R., Pidoplichko, V. I., Broide, R. S., & Dani, J. A. (2003). Differential desensitization and distribution of nicotinic acetylcholine receptor subtypes in midbrain dopamine areas. Journal of Neuroscience, 23(8), 3176–3185.Google Scholar
  173. Woolverton, W. L., & Johnson, K. M. (1992). Neurobiology of cocaine abuse. Trends in Pharmacological Sciences, 13(5), 193–200.Google Scholar
  174. Wrase, J., Schlagenhauf, F., Kienast, T., Wustenberg, T., Bermpohl, F., Kahnt, T., et al. (2007). Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. NeuroImage, 35(2), 787–794.Google Scholar
  175. Yahyavi-Firouz-Abadi, N., & See, R. E. (2009). Anti-relapse medications: Preclinical models for drug addiction treatment. Pharmacology & Therapeutics, 124(2), 235–247.Google Scholar

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© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Centre for Neuropsychopharmacology, Division of Brain Sciences, Department of MedicineImperial College LondonLondonUK

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