Introduction: Addiction and Brain Reward and Anti-Reward Pathways (2024)

1. Gardner EL. Brain reward mechanisms. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG, editors. Substance Abuse: A Comprehensive Textbook. 4th edn. Philadelphia: Lippincott Williams & Wilkins; 2005. pp. 48–97. [Google Scholar]

2. Gardner EL. What we have learned about addiction from animal models of drug self-administration. Am J Addict. 2000;9:285–313. [PubMed] [Google Scholar]

3. O’Brien CP, Gardner EL. Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol Ther. 2005;108:18–58. [PubMed] [Google Scholar]

4. Gardner EL, David J. The neurobiology of chemical addiction. In: Elster J, Skog O-J, editors. Getting Hooked: Rationality and the Addictions. Cambridge, England: Cambridge University Press; 1999. pp. 93–136. [Google Scholar]

5. Wise RA, Gardner EL. Functional anatomy of substance-related disorders. In: D'haenen H, den Boer JA, Willner P, editors. Biological Psychiatry. New York: Wiley; 2002. pp. 509–522. [Google Scholar]

6. Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol. 1954;47:419–427. [PubMed] [Google Scholar]

7. Olds J. Pleasure centers in the brain. Sci Am. 1956;95(4):105–116. [Google Scholar]

8. Olds J. Hypothalamic substrates of reward. Physiol Rev. 1962;42:554–604. [PubMed] [Google Scholar]

9. Olds ME, Olds J. Approach-avoidance analysis of rat diencephalon. J Comp Neurol. 1963;120:259–295. [PubMed] [Google Scholar]

10. Olds ME, Olds J. Drives, rewards and the brain. In: Newcomb TM, editor. New Directions in Psychology. New York: Holt, Rinehart & Winston; 1965. pp. 329–410. [Google Scholar]

11. Routtenberg A, Gardner EL, Huang YH. Self-stimulation pathways in the monkey, Macaca mulatta. Exp Neurol. 1971;33:213–224. [PubMed] [Google Scholar]

12. Gallistel CR, Shizgal P, Yeomans JS. A portrait of the substrate for self-stimulation. Psychol Rev. 1981;88:228–273. [PubMed] [Google Scholar]

13. Wise RA, Bozarth MA. Brain reward circuitry: four circuit elements “wired” in apparent series. Brain Res Bull. 1984;12:203–208. [PubMed] [Google Scholar]

14. Stuber GD, van Leeuwen WA, Sparta DR, Zhang F, Deisseroth K, Bonci A. Optogenetic control of brain reward circuitry. Paper presented at meetings of the Society for Neuroscience; October 2009; Chicago. 2009. (Abstract published in 2009 Abstract Viewer/Itinerary Planner CD-ROM, the Thirty-Ninth Annual Meeting of the Society for Neuroscience, Chicago, October 17–21, 2009, Society for Neuroscience, Washington: DC, Abstract Number 686.8) [Google Scholar]

15. Alheid GF, Heimer L. New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia inominata. Neuroscience. 1988;27:1–39. [PubMed] [Google Scholar]

16. Hubner CB, Koob GF. The ventral pallidum plays a role in mediating cocaine and heroin self-administration in the rat. Brain Res. 1990;508:20–29. [PubMed] [Google Scholar]

17. Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci. 1992;13:177–184. [PubMed] [Google Scholar]

18. Kalivas PW, Churchill L, Klitenick MA. The circuitry mediating the translation of motivational stimuli into adaptive motor responses. In: Kalivas PW, Barnes CD, editors. Limbic Motor Circuits and Neuropsychiatry. Boca Raton, Florida: CRC Press; 1993. pp. 237–287. [Google Scholar]

19. Napier TC. Transmitter actions and interactions on pallidal neuronal function. In: Kalivas PW, Barnes CD, editors. Limbic Motor Circuits and Neuropsychiatry. Boca Raton, Florida: CRC Press; 1993. pp. 124–153. [Google Scholar]

20. Gong WH, Neill D, Justice JB., Jr Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum. Brain Res. 1996;707:64–74. [PubMed] [Google Scholar]

21. Hasenrohrl RU, Frisch C, Huston JP. Evidence for anatomical specificity for the reinforcing effects of SP in the nucleus basalis magnocellularis region. Neuroreport. 1998;9:7–10. [PubMed] [Google Scholar]

22. McBride WJ, Murphy JM, Ikemoto S. Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res. 1999;101:129–152. [PubMed] [Google Scholar]

23. White NM, Milner PM. The psychobiology of reinforcers. Annu Rev Psychol. 1992;43:443–471. [PubMed] [Google Scholar]

24. Robbins TW, Everitt BJ. Drug addiction: bad habits add up. Nature. 1999;398:567–570. [PubMed] [Google Scholar]

25. Garavan H, Pankiewicz J, Bloom A, Cho J-K, Sperry L, Ross TJ, Salmeron BJ, Risinger R, Kelley D, Stein EA. Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry. 2000;157:1789–1798. [PubMed] [Google Scholar]

26. Higgins JW, Mahl GF, Delgado JMR, Hamlin H. Behavioral changes during intracerebral electrical stimulation. AMA Arch Neurol Psychiatry. 1956;76:399–419. [PubMed] [Google Scholar]

27. Delgado JMR, Hamlin H. Spontaneous and evoked electrical seizures in animals and in humans. In: Ramey ER, O'Doherty DS, editors. Electrical Studies on the Unanesthetized Brain. New York: Harper (Hoeber Medical Division); 1960. pp. 133–158. [Google Scholar]

28. Heath RG, Mickle WH. Evaluation of seven years' experience with depth electrode studies in human patients. In: Ramey ER, O'Doherty DS, editors. Electrical Studies on the Unanesthetized Brain. New York: Harper (Hoeber Medical Division); 1960. pp. 214–247. [Google Scholar]

29. Sem-Jacobsen W, Torkildsen A. Depth recording and electrical stimulation in the human brain. In: Ramey ER, O'Doherty DS, editors. Electrical Studies on the Unanesthetized Brain. New York: Harper (Hoeber Medical Division); 1960. pp. 280–288. [Google Scholar]

30. Bishop MP, Elder ST, Heath RG. Intracranial self-stimulation in man. Science. 1963;140:394–396. [PubMed] [Google Scholar]

31. Heath RG. Electrical self-stimulation of the brain in man. Am J Psychiatry. 1963;120:571–577. [PubMed] [Google Scholar]

32. Stein L, Ray OS. Brain stimulation reward "thresholds" self-determined in rat. Psychopharmacologia (Berl) 1960;1:251–2566. [PubMed] [Google Scholar]

33. Gardner EL. An improved technique for determining brain reward thresholds in primates. Behav Res Methods Instrum. 1971;3:273–274. [Google Scholar]

34. Miliaressis E, Rompré P-P, Laviolette P, Philippe L, Coulombe D. The curve-shift paradigm in self-stimulation. Physiol Behav. 1986;37:85–91. [PubMed] [Google Scholar]

35. Coulombe D, Miliaressis E. Fitting intracranial self-stimulation data with growth models. Behav Neurosci. 1987;101:209–214. [PubMed] [Google Scholar]

36. Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: basic findings from the National Comorbidity Survey. Exp Clin Psychol. 1994;2:244–268. [Google Scholar]

37. Vorel SR, Ashby CR, Jr, Paul M, Liu X, Hayes R, Hagan JJ, Middlemiss DN, Stemp G, Gardner EL. Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats. J Neurosci. 2002;22:9595–9603. [PMC free article] [PubMed] [Google Scholar]

38. Pak AC, Ashby CR, Jr, Heidbreder CA, Pilla M, Gilbert J, Xi Z-X, Gardner EL. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions. Int J Neuropsychopharmacol. 2006;9:585–602. [PMC free article] [PubMed] [Google Scholar]

39. Spiller K, Xi Z-X, Peng X-Q, Newman AH, Ashby CR, Jr, Heidbreder CA, Gaál J, Gardner EL. The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain-stimulation reward in rats. Psychopharmacology. 2008;196:533–542. [PMC free article] [PubMed] [Google Scholar]

40. Xi Z-X, Spiller K, Pak AC, Gilbert J, Dillon C, Li X, Peng X-Q, Gardner EL. Cannabinoid CB1 receptor antagonists attenuate cocaine’s rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Neuropsychopharmacology. 2008;33:1735–1745. [PubMed] [Google Scholar]

41. Li X, Li J, Peng X-Q, Spiller K, Gardner EL, Xi Z-X. Metabotropic glutamate receptor 7 modulates cocaine’s rewarding effects in rats: involvement of a ventral pallidal GABAergic mechanism. Neuropsychopharmacology. 2009;34:1783–1796. [PMC free article] [PubMed] [Google Scholar]

42. Gardner EL, Lowinson JH. Drug craving and positive/negative hedonic brain substrates activated by addicting drugs. Semin Neurosci. 1993;5:359–368. [Google Scholar]

43. Xi Z-X, Spiller K, Gardner EL. Cannabinoid CB1 and CB2 receptors modulate brain reward function in opposite directions in rats. Paper presented at meetings of the Society for Neuroscience; October 2009; Chicago. (Abstract published in 2009 Abstract Viewer/Itinerary Planner CD-ROM, the Thirty-Ninth Annual Meeting of the Society for Neuroscience, Chicago, Illinois, October 17–21, 2009, Society for Neuroscience, Washington, DC, Abstract Number 449.13) 2009. [Google Scholar]

44. Tzschentke TM. Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol. 1998;56:613–672. [PubMed] [Google Scholar]

45. Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol. 2007;12:227–462. [PubMed] [Google Scholar]

46. Gardner EL, Wise RA. Animal models of addiction. In: Charney DS, Nestler EJ, editors. Neurobiology of Mental Illness. 3rd edn. Oxford, England: Oxford University Press; 2009. pp. 757–774. [Google Scholar]

47. Yokel RA, Wise RA. Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science. 1975;187:547–549. [PubMed] [Google Scholar]

48. Gardner EL, Chen J, Paredes W. Overview of chemical sampling techniques. J Neurosci Methods. 1993;48:173–197. [PubMed] [Google Scholar]

49. Wise RA. In vivo estimates of extracellular dopamine and dopamine metabolite levels during intravenous cocaine or heroin self-administration. Semin Neurosci. 1993;5:337–342. [Google Scholar]

50. Wise RA, Leone P, Rivest R, Leeb K. Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self-administration. Synapse. 1995;21:140–148. [PubMed] [Google Scholar]

51. Wise RA, Newton P, Leeb K, Burnette B, Poco*ck D, Justice JB., Jr Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology. 1995;120:10–20. [PubMed] [Google Scholar]

52. Solomon RL, Corbit JD. An opponent-process theory of motivation. I. Temporal dynamics of affect. Psychol Rev. 1974;81:119–145. [PubMed] [Google Scholar]

53. Solomon RL. The opponent-process theory of acquired motivation: the costs of pleasure and the benefits of pain. Am Psychologist. 1980;35:691–712. [PubMed] [Google Scholar]

54. Solomon RL. Recent experiments testing an opponent-process theory of acquired motivation. Acta Neurobiol Exp (Warsaw) 1980;40:271–289. [PubMed] [Google Scholar]

55. Koob GF, Stinus L, Le Moal M, Bloom FE. Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence. Neurosci Biobehav Rev. 1989;13:135–140. [PubMed] [Google Scholar]

56. Koob GF, Caine SB, Parsons L, Markou A, Weiss F. Opponent process model and psychostimulant addiction. Pharmacol Biochem Behav. 1997;57:513–521. [PubMed] [Google Scholar]

57. Koob GF, Le Moal M. Neurobiological mechanisms for opponent motivational processes in addiction. Philoso Trans R Soc B. 2008;363:3113–3123. [PMC free article] [PubMed] [Google Scholar]

58. Nazzaro JM, Seeger TF, Gardner EL. Morphine differentially affects ventral tegmental and substantia nigra brain reward thresholds. Pharmacol Biochem Behav. 1981;14:325–331. [PubMed] [Google Scholar]

59. Broderick PA, Gardner EL, van Praag HM. In vivo electrochemical evidence for a differential enkephalinergic modulation of dopamine in rat nigrostriatal and mesolimbic systems: correlated behavioral stereotypy results. Paper presented at meetings of the International Narcotic Research Conference; June 1983; Garmisch-Partenkirchen, Germany. [Google Scholar]

60. Broderick PA, Gardner EL, van Praag HM. In vivo electrochemical and behavioral evidence for specific neural substrates modulated differentially by enkephalin in rat stimulant stereotypy and locomotion. Biol Psychiatry. 1984;19:45–54. [PubMed] [Google Scholar]

61. Kokkinidis L, McCarter BD. Postcocaine depression and sensitization of brain-stimulation reward: analysis of reinforcement and performance effects. Pharmacol Biochem Behav. 1990;36:463–471. [PubMed] [Google Scholar]

62. Markou A, Koob GF. Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology. 1991;4:17–26. [PubMed] [Google Scholar]

63. Schulteis G, Markou A, Cole M, Koob GF. Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci USA. 1995;92:5880–5884. [PMC free article] [PubMed] [Google Scholar]

64. Gardner EL, Lepore M. Withdrawal from a SINGLE small dose of marijuana elevates baseline brain-stimulation reward thresholds in rats. Paper presented at Winter Conference on Brain Research; January 1996; Aspen, Colorado. [Google Scholar]

65. Epping-Jordan MP, Watkins SS, Koob GF, Markou A. Dramatic decreases in brain reward function during nicotine withdrawal. Nature. 1998;393:76–79. [PubMed] [Google Scholar]

66. Blum K, Cull JG, Braverman ER, Comings DE. Reward deficiency syndrome. Am Scientist. 1996;84:132–145. [Google Scholar]

67. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJH, Cull JG, Comings DE. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996;89:396–400. [PMC free article] [PubMed] [Google Scholar]

68. Gardner EL, Blum K. Neurobiology and genetics of addiction: implications of “reward deficiency syndrome” for therapeutic strategies in chemical dependency. Paper presented at Russell Sage Foundation Conference on Addiction; June 1997; New York. [Google Scholar]

69. Gardner EL. Neurobiology and genetics of addiction: implications of “reward deficiency syndrome” for therapeutic strategies in chemical dependency. In: Elster J, editor. Addiction: Entries and Exits. New York: Russell Sage Foundation; 1999. pp. 57–119. [Google Scholar]

70. Comings DE, Blum K. Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res. 2000;126:325–341. [PubMed] [Google Scholar]

71. Gardner EL. Reward behaviors as a function of hypo-dopaminergic activity: animal models of reward deficiency syndrome. Mol Psychiatry. 2001;6(suppl. 1):S4. [Google Scholar]

72. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jadadeeswaran P, Nogami H, Briggs AH, Cohn JB. Allelic association of the human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263:2055–2059. [PubMed] [Google Scholar]

73. Volkow ND, Wang G-J, Fowler JS, Logan J, Gatley SJ, Gifford A, Hitzemann R, Ding Y-S, Pappas N. Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. Am J Psychiatry. 1999;156:1440–1443. [PubMed] [Google Scholar]

74. Volkow ND, Fowler JS, Wang G-J, Ding Y-S, Gatley SJ. Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: results from imaging studies. Eur Neuropsychopharmacol. 2002;12:557–566. [PubMed] [Google Scholar]

75. Volkow ND, Wang G-J, Fowler JS, Thanos PP, Logan J, Gatley SJ, Gifford A, Ding Y-S, Wong C, Pappas N. Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study. Synapse. 2002;46:79–82. [PubMed] [Google Scholar]

76. Volkow ND, Wang G-J, Telang F, Fowler JS, Logan J, Jayne M, Ma Y, Pradhan K, Wong C. Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci. 2007;27:12700–12706. [PMC free article] [PubMed] [Google Scholar]

77. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA. Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci. 2002;5:169–174. [PubMed] [Google Scholar]

78. Dalley JW, Fryer TD, Brichard L, Robinson ESJ, Theobald DEH, Lääne K, Peña Y, Murphy ER, Shah Y, Probst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron J-C, Everitt BJ, Robbins TW. Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science. 2007;315:1267–1270. [PMC free article] [PubMed] [Google Scholar]

79. Staley JK, Mash DC. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci. 1996;16:6100–6106. [PMC free article] [PubMed] [Google Scholar]

80. Mash DC. Are neuroadaptations in D3 dopamine receptors linked to the development of cocaine dependence? Mol Psychiatry. 1997;2:7–8. [PubMed] [Google Scholar]

81. Gardner EL. Use of animal models to develop antiaddiction medications. Curr Psychiat Rep. 2008;10:377–384. [PMC free article] [PubMed] [Google Scholar]

82. Xi Z-X, Gardner EL. Hypothesis-driven medication discovery for the treatment of psychostimulant addiction. Curr Drug Abuse Rev. 2008;1:303–327. [PMC free article] [PubMed] [Google Scholar]

83. Xi Z-X, Spiller K, Gardner EL. Mechanism-based medication development for the treatment of nicotine dependence. Acta Pharmacol Sin. 2009;30:723–739. [PMC free article] [PubMed] [Google Scholar]

84. Heidbreder CA, Gardner EL, Xi Z-X, Thanos PK, Mugnaini M, Hagan JJ, Ashby Cr., Jr The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence. Brain Res Rev. 2005;49:77–105. [PMC free article] [PubMed] [Google Scholar]

85. Heidbreder CA, Andreoli M, Marcon C, Hutcheson DM, Gardner EL, Ashby CR., Jr Evidence for the role of dopamine D3 receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice. Addict Biol. 2007;12:35–50. [PubMed] [Google Scholar]

86. Beitner-Johnson D, Guitart X, Nestler EJ. Dopaminergic brain reward regions of Lewis and Fischer rats display different levels of tyrosine hydroxylase and other morphine- and cocaine-regulated phosphoproteins. Brain Res. 1991;561:147–150. [PubMed] [Google Scholar]

87. Guitart X, Beitner-Johnson D, Marby DW, Kosten TA, Nestler EJ. Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse. 1992;12:242–253. [PubMed] [Google Scholar]

88. Berrettini WH, Ferraro TN, Alexander RC, Buchberg AM, Vogel WH. Quantitative trait loci mapping of three loci controlling morphine preference using inbred mouse strains. Nat Genet. 1994;7:54–58. [PubMed] [Google Scholar]

89. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology. 1997;132:107–124. [PubMed] [Google Scholar]

90. Brodkin ES, Carlezon WA, Jr, Haile CN, Kosten TA, Heninger GR, Nestler EJ. Genetic analysis of behavioral, neuroendocrine, and biochemical parameters in inbred rodents: initial studies in Lewis and Fischer 344 rats and in A/J and C57BL/6J mice. Brain Res. 1998;805:55–68. [PubMed] [Google Scholar]

91. McBride WJ, Li TK. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol. 1998;12:339–369. [PubMed] [Google Scholar]

92. Crabbe JC, Phillips TJ, Buck KJ, Cunningham CL, Belknap JK. Identifying genes for alcohol and drug sensitivity: recent progress and future directions. Trends Neurosci. 1999;22:173–179. [PubMed] [Google Scholar]

93. Nestler EJ. Genes and addiction. Nat Genet. 2000;26:277–281. [PubMed] [Google Scholar]

94. Dole VP, Nyswander M. A medical treatment for diacetylmorphine (heroin) addiction. A clinical trial with methadone hydrochloride. JAMA. 1965;193:646–650. [PubMed] [Google Scholar]

95. Dole VP, Nyswander ME, Kreek MJ. Narcotic blockade - A medical technique for stopping heroin use by addicts. Trans Assoc Am Physicians. 1966;79:122–136. [PubMed] [Google Scholar]

96. Wise RA. The dopamine synapse and the notion of “pleasure centers” in the brain. Trends Neurosci. 1980;3:91–95. [Google Scholar]

97. Lee R-S, Criado JE, Koob GF, Henriksen SJ. Cellular responses of nucleus accumbens neurons to opiate-seeking behavior. I. Sustained responding during heroin self-administration. Synapse. 1999;33:49–58. [PubMed] [Google Scholar]

98. Schultz W, Apicella P, Scarnati E, Ljungberg T. Neuronal activity in monkey ventral striatum related to the expectation of reward. J Neurosci. 1992;12:4595–4610. [PMC free article] [PubMed] [Google Scholar]

99. Chang J-Y, Sawyer SF, Lee R-S, Woodward DJ. Electrophysiological and pharmacological evidence for the role of the nucleus accumbens in cocaine self-administration in freely moving rats. J Neurosci. 1994;14:1224–1244. [PMC free article] [PubMed] [Google Scholar]

100. Kobayashi S, Schultz W. Influence of reward delays on responses of dopamine neurons. J Neurosci. 2008;28:7837–7846. [PMC free article] [PubMed] [Google Scholar]

101. Gregorios-Pippas L, Tobler PN, Schultz W. Short-term temporal discounting of reward value in human ventral striatum. J Neurophysiol. 2009;101:1507–1523. [PMC free article] [PubMed] [Google Scholar]

102. Hare TA, O’Doherty J, Camerer CF, Schultz W, Rangel A. Dissociating the role of the orbitalfrontal cortex and the striatum in the computation of goal values and prediction errors. J Neurosci. 2008;28:5623–5630. [PMC free article] [PubMed] [Google Scholar]

103. Peoples LL, Uzwiak AJ, Gee F, Fabbricatore AT, Muccino KJ, Mohta BD, West MO. Phasic accumbal firing may contribute to the regulation of drug taking during intravenous cocaine self-administration sessions. Ann NY Acad Sci. 1999;877:781–787. [PubMed] [Google Scholar]

104. Peoples LL, Cavanaugh D. Differential changes in signal and background firing of accumbal neurons during cocaine self-administration. J Neurophysiol. 2003;90:993–10101. [PubMed] [Google Scholar]

105. Uhl GR. Molecular genetics of substance abuse vulnerability: remarkable recent convergence of genome scan results. Ann NY Acad Sci. 2004;1025:1–13. [PubMed] [Google Scholar]

106. Uhl GR, Drgan T, Johnson C, Fatusin OO, Liu Q-R, Contoreggi C, Li C-Y, Buck K, Crabbe J. “Higher order” addiction molecular genetics: convergent data from genome-wide association in humans and mice. Biochem Pharmacol. 2008;75:98–111. [PMC free article] [PubMed] [Google Scholar]

107. Khokhar JY, Ferguson CS, Zhu AZX, Tyndale RF. Pharmacogenetics of drug dependence: role of gene variations in susceptibility and treatment. Annu Rev Pharmacol Toxicol. 2010;50:39–61. [PubMed] [Google Scholar]

108. Piazza PV, Maccari S, Deminière JM, Le Moal M, Mormède P, Simon H. Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci USA. 1991;88:2088–2092. [PMC free article] [PubMed] [Google Scholar]

109. Deminière JM, Piazza PV, Guegan G, Abrous N, Maccari S, Le Moal M, Simon H. Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers. Brain Res. 1992;586:135–139. [PubMed] [Google Scholar]

110. Redolat R, Pérez-Martinez A, Carrasco MC, Mesa P. Individual differences in novelty-seeking and behavioral responses to nicotine: a review of animal studies. Curr Drug Abuse Rev. 2009;2:230–242. [PubMed] [Google Scholar]

111. Sher KJ, Bartholow BD, Wood MD. Personality and substance use disorders: a prospective study. J Consult Clin Psychol. 2000;68:818–829. [PubMed] [Google Scholar]

112. Zuckerman M, Kuhlman DM. Personality and risk-taking: common biosocial factors. J Pers. 2000;68:999–1029. [PubMed] [Google Scholar]

113. Mitchell SH. Measuring impulsivity and modeling its association with cigarette smoking. Behav Cogn Neurosci Rev. 2004;3:261–275. [PubMed] [Google Scholar]

114. Perkins KA, Lerman C, Coddington SB, Jetton C, Karelitz JL, Scott JA, Wilson AS. Initial nicotine sensitivity in humans as a function of impulsivity. Psychopharmacology. 2008;200:529–544. [PubMed] [Google Scholar]

115. Crowley TJ, Mikulich SK, Macdonald M, Young SE, Zerbe GO. Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome. Drug Alcohol Depend. 1998;49:225–237. [PubMed] [Google Scholar]

116. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith D, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse. JAMA. 1990;264:2511–2518. [PubMed] [Google Scholar]

117. Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC. Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;53:232–240. [PubMed] [Google Scholar]

118. Wilson JJ, Levin FR. Attention deficit hyperactivity disorder (ADHD) and substance use disorders. Curr Psychiat Rep. 2001;3:497–506. [PubMed] [Google Scholar]

119. Wilens TE. Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship, subtypes at risk, and treatment issues. Psychiat Clin North Am. 2004;27:283–301. [PubMed] [Google Scholar]

120. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001;24:97–129. [PubMed] [Google Scholar]

121. Koob GF, Ahmed SH, Boutrel B, Chen SA, Kenny PJ, Markou A, O'Dell LE, Parsons LH, Sanna PP. Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev. 2004;27:739–749. [PubMed] [Google Scholar]

122. Koob GF. Hedonic homeostatic dysregulation as a driver of drug-seeking behavior. Drug Discov Today Dis Models. 2008;5:207–215. [PMC free article] [PubMed] [Google Scholar]

123. Lepore M, Vorel R, Gardner EL. Studies on the neurobiological interrelationship between vulnerability to depression and vulnerability to drug abuse in animal models. Behav Pharmacol. 1995;6([suppl. 1]):82–84. [Google Scholar]

124. Phillips GD, Howes SR, Whitelaw RB, Robbins TW, Everitt BJ. Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists. Psychopharmacology. 1994;115:419–429. [PubMed] [Google Scholar]

125. Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Buchheimer N, Ehrenkaufer R, Mach RH. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci. 2006;9:1050–1056. [PubMed] [Google Scholar]

126. Ginovart N, Farde L, Halldin C, Swahn CG. Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates. Synapse. 1999;31:154–162. [PubMed] [Google Scholar]

127. Ginovart N, Wilson AA, Houle S, Kapur S. Amphetamine pretreatment induces a change in both D2 -receptor density and apparent affinity: a [11C]raclopride positron emission tomography study in cats. Biol Psychiatry. 2004;55:1188–1194. [PubMed] [Google Scholar]

128. Lee B, London ED, Poldrack RA, Farahi J, Nacca A, Monterosso JR, Mumford JA, Bokarius AV, Dahlbom M, Mukherjee J, Bilder RM, Brody AL, Mandelkern MA. Striatal dopamine D2/D3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J Neurosci. 2009;29:14734–14740. [PMC free article] [PubMed] [Google Scholar]

129. Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ. High impulsivity predicts the switch to compulsive cocaine-taking. Science. 2008;320:1352–1355. [PMC free article] [PubMed] [Google Scholar]

130. Di Chiara G, Bassareo V, Fenu S, De Luca MA, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D. Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology. 2004;47(suppl.1):227–241. [PubMed] [Google Scholar]

131. Wise RA. Dopamine, learning and motivation. Nat Rev Neurosci. 2004;5:483–494. [PubMed] [Google Scholar]

132. Ikemoto S, Qin M, Liu Z-H. The functional divide for primary reinforcement of D-amphetamine lies between the medial and lateral ventral striatum: is the division of the nucleus accumbens core, shell, and olfactory tubercle valid? J Neurosci. 2005;25:5061–5065. [PMC free article] [PubMed] [Google Scholar]

133. Tiffany ST. A cognitive model of drug urges and drug-use behavior: role of automatic and non-automatic processes. Psychol Rev. 1990;97:146–168. [PubMed] [Google Scholar]

134. O’Brien CP, McLellan AT. Myths about the treatment of addiction. Lancet. 1996;347:237–240. [PubMed] [Google Scholar]

135. Everitt BJ, Dickinson A, Robbins TW. The neuropsychological basis of addictive behaviour. Brain Res Rev. 2001;36:129–138. [PubMed] [Google Scholar]

136. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8:1481–1489. [PubMed] [Google Scholar]

137. Verdejo-García A, Pérez-García M. Substance abusers= self-awareness of the neurobehavioral consequences of addiction. Psychiat Res. 2008;158:172–180. [PubMed] [Google Scholar]

138. Goldstein R, Craig AD, Bechara A, Garavan H, Childress AR, Paulus MP, Volkow ND. The neurocircuitry of impaired insight in drug addiction. Trends Cogn Sci. 2009;13:372–380. [PMC free article] [PubMed] [Google Scholar]

139. Childress AR, Hole AV, Ehrman RN, Robbins SJ, McLellan AT, O’Brien CP. Cue reactivity and cue reactivity interventions in drug dependence. NIDA Res Monogr. 1993;137:73–95. [PubMed] [Google Scholar]

140. Leshner AI. Addiction is a brain disease, and it matters. Science. 1997;278:45–47. [PubMed] [Google Scholar]

141. O’Brien CP, Childress AR, Ehrman R, Robbins SJ. Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol. 1998;12:15–22. [PubMed] [Google Scholar]

142. Robbins TW, Everitt BJ. Limbic-striatal memory systems and drug addiction. Neurobiol Learn Mem. 2002;78:625–636. [PubMed] [Google Scholar]

143. White NM. Some highlights of research on the effects of caudate nucleus lesions over the past 200 years. Behav Brain Res. 2009;199:3–23. [PubMed] [Google Scholar]

144. Haber SN, Fudge JL, McFarland NR. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci. 2000;20:2369–2382. [PMC free article] [PubMed] [Google Scholar]

145. Everitt BJ, Belin D, Economidou D, Pelloux Y, Dalley JW, Robbins TW. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos Trans R Soc B. 2008;363:3125–3135. [PMC free article] [PubMed] [Google Scholar]

146. Letchworth SR, Nader MA, Smith HR, Friedman DP, Porrino LJ. Progression of changes in dopamine transporter binding site density as a result of cocaine self-administration in rhesus monkeys. J Neurosci. 2001;21:2799–2807. [PMC free article] [PubMed] [Google Scholar]

147. Porrino LJ, Daunais JB, Smith HR, Nader MA. The expanding effects of cocaine: studies in a nonhuman primate model of cocaine self-administration. Neurosci Biobehav Rev. 2004;27:813–820. [PubMed] [Google Scholar]

148. Volkow ND, Wang G-J, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma YM, Wong C. Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci. 2006;26:6583–6588. [PMC free article] [PubMed] [Google Scholar]

149. Takahashi Y, Roesch MR, Stalnaker TA, Schoenbaum G. Cocaine shifts the balance of associative encoding from ventral to dorsolateral striatum. Front Integr Neurosci. 2007;1:11. [Published online 30 Dec 2007; see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526005] [PMC free article] [PubMed] [Google Scholar]

150. Bozarth MA, Wise RA. Anatomically distinct opiate receptor fields mediate reward and physical dependence. Science. 1984;224:516–517. [PubMed] [Google Scholar]

151. Pert A, Yaksh T. Sites of morphine induced analgesia in the primate brain: relation to pain pathways. Brain Res. 1974;80:135–140. [PubMed] [Google Scholar]

152. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–979. [PubMed] [Google Scholar]

153. Schaible HG. Peripheral and central mechanisms of pain generation. Handb Exp Pharmacol. 2007;177:3–28. [PubMed] [Google Scholar]

154. D’Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth. 2008;101:8–16. [PubMed] [Google Scholar]

155. Alcoholics Anonymous. Alcoholics Anonymous Big Book. 1st edn. New York: Alcoholics Anonymous World Services, Inc.; 1939. [Google Scholar]

156. Shalev U, Grimm JW, Shaham Y. Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev. 2002;54:1–42. [PubMed] [Google Scholar]

157. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology. 2003;168:3–20. [PubMed] [Google Scholar]

158. Aguilar MA, Rodríguez-Arias M, Miñarro J. Neurobiological mechanisms of the reinstatement of drug-conditioned place preference. Brain Res Rev. 2009;59:253–277. [PubMed] [Google Scholar]

159. Epstein DH, Preston KL. The reinstatement model and relapse prevention: a clinical perspective. Psychopharmacology. 2003;168:31–41. [PMC free article] [PubMed] [Google Scholar]

160. Epstein DH, Preston KL, Stewart J, Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology. 2006;189:1–16. [PMC free article] [PubMed] [Google Scholar]

161. Stewart J. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. J Psychiatry Neurosci. 2000;25:125–136. [PMC free article] [PubMed] [Google Scholar]

162. Moore RY, Bloom FE. Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci. 1979;2:113–168. [PubMed] [Google Scholar]

163. Itoi K. Ablation of the central noradrenergic neurons for unraveling their roles in stress and anxiety. Ann NY Acad Sci. 2008;1129:47–54. [PubMed] [Google Scholar]

164. Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL. Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science. 2001;292:1175–1178. [PubMed] [Google Scholar]

165. Hayes RJ, Vorel SR, Spector J, Liu X, Gardner EL. Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat. Psychopharmacology. 2003;168:75–83. [PubMed] [Google Scholar]

166. Koob GF. Stress, corticotropin-releasing factor, and drug addiction. Ann NY Acad Sci. 1999;897:27–45. [PubMed] [Google Scholar]

167. Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 2007;30:399–406. [PMC free article] [PubMed] [Google Scholar]

168. Koob GF, Zorrilla EP. Neurobiological mechanisms of addiction: focus on corticotropin-releasing factor. Curr Opin Investig Drugs. 2010;11:63–71. [PMC free article] [PubMed] [Google Scholar]

169. Grimm JW, Hope BT, Wise RA, Shaham Y. Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature. 2001;412:141–142. [PMC free article] [PubMed] [Google Scholar]

170. Grimm JW, Lu L, Hayashi T, Hope BT, Su T-P, Shaham Y. Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. J Neurosci. 2003;23:742–747. [PMC free article] [PubMed] [Google Scholar]

171. Lu L, Hope BT, Dempsey J, Liu SY, Bossert JM, Shaham Y. Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nat Neurosci. 2005;8:212–219. [PubMed] [Google Scholar]

172. Lu L, Uejima JL, Gray SM, Bossert JM, Shaham Y. Systemic and central amygdala injections of the mGluR2/3 agonist LY379268 attenuate the expression of incubation of cocaine craving. Biol Psychiatry. 2007;61:591–598. [PubMed] [Google Scholar]

173. Xi Z-X, Gilbert J, Campos AC, Kline N, Ashby CR, Jr, Hagan JJ, Heidbreder CA, Gardner EL. Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats. Psychopharmacology. 2004;176:57–65. [PMC free article] [PubMed] [Google Scholar]

174. Hebb DO. The Organization of Behavior: A Neuropsychological Theory. New York: Wiley; 1949. [Google Scholar]

175. Chen BT, Hopf W, Bonci A. Synaptic plasticity in the mesolimbic system: therapeutic implications for substance abuse. Ann NY Acad Sci. 2010;1187:129–139. [PMC free article] [PubMed] [Google Scholar]

176. Thomas MJ, Beurrier C, Bonci A, Malenka RC. Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci. 2001;4:1217–1223. [PubMed] [Google Scholar]

177. Hoffman AF, Oz M, Caulder T, Lupica CR. Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid Exposure. J Neurosci. 2003;23:4815–4820. [PMC free article] [PubMed] [Google Scholar]

178. Fourgeaud L, Mato S, Bouchet D, Hémar A, Worley PF, Manzoni OJ. A single in vivo exposure to cocaine abolishes endocannabinoid-mediated long-term depression in the nucleus accumbens. J Neurosci. 2004;24:6939–6945. [PMC free article] [PubMed] [Google Scholar]

179. Liu Q-S, Pu L, Poo M-M. Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature. 2005;437:1027–1031. [PMC free article] [PubMed] [Google Scholar]

180. Tye KM, Stuber GD, de Ridder B, Bonci A, Janak PH. Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning. Nature. 2008;453:1253–1258. [PMC free article] [PubMed] [Google Scholar]

181. Rademacher DJ, Rosenkranz JA, Morshedi MM, Sullivan EM, Meredith GE. Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala. J Neurosci. 2010;30:4676–4686. [PMC free article] [PubMed] [Google Scholar]

182. Pu L, Bao G-B, Xu N-J, Ma L, Pei G. Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates. J Neurosci. 2002;22:1914–1921. [PMC free article] [PubMed] [Google Scholar]

183. Thompson AM, Swant J, Gosnell BA, Wagner JJ. Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration. Neuroscience. 2004;127:177–185. [PubMed] [Google Scholar]

184. Kenney JW, Gould TJ. Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol. 2008;38:101–121. [PMC free article] [PubMed] [Google Scholar]

185. Kasanetz F, Deroche-Gamonet V, Berson N, Balado E, Lafourcade M, Manzoni O, Piazza PV. Transition to addiction is associated with a persistent impairment in synaptic plasticity. Science. 2010;328:1709–1712. [PubMed] [Google Scholar]

186. Gardner EL. Pain management and the so-called “risk” of addiction. In: Smith H, Passik SD, editors. Pain and Chemical Dependency. London: Oxford University Press; 2008. pp. 427–435. [Google Scholar]

187. Narita M, Kishimoto Y, Ise Y, Yajima Y, Misawa K, Suzuki T. Direct evidence for the involvement of the mesolimbic κ-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state. Neuropsychopharmacology. 2005;30:11–118. [PubMed] [Google Scholar]

188. Ozaki S, Narita M, Narita M, Ozaki M, Khotib J, Suzuki T. Role of extracellular signal-regulated kinase in the ventral tegmental area in the suppression of the morphine-induced rewarding effect in mice with sciatic nerve ligation. J Neurochem. 2004;88:1389–1397. [PubMed] [Google Scholar]

189. Kinshore KR, Desiraju T. Inhibition of positively rewarding behavior by the heightened aggressive state evoked either by pain-inducing stimulus or septal lesion. Indian J Physiol Pharmacol. 1990;34:125–129. [PubMed] [Google Scholar]

190. Vaccarino AL, Marek P, Kest B, Ben-Eliyahu S, Couret LC, Jr, Kao B, Liebeskind JC. Morphine fails to produce tolerance when administered in the presence of formalin pain in rats. Brain Res. 1993;627:287–290. [PubMed] [Google Scholar]

191. UNAIDS (Joint United Nations Programme on HIV/AIDS) Cancer Pain Relief, with a Guide to Opioid Availability. 2nd edn. Geneva, Switzerland: World Health Organization; 1996. pp. 24–37. [Google Scholar]

192. Stotts AL, Dodrill CL, Kosten TR. Opioid dependence treatment: options in pharmacotherapy. Expert Opin Pharmacother. 2009;10:1727–1740. [PMC free article] [PubMed] [Google Scholar]

193. Lobmaier P, Gossop M, Waal H, Bramness J. The pharmacological treatment of opioid addiction - a clinical perspective. Eur J Clin Pharmacol. 2010;66:537–545. [PubMed] [Google Scholar]

194. Wakhlu S. Buprenorphine: a review. J Opioid Manag. 2009;5:59–64. [PubMed] [Google Scholar]

195. Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, Williams H, Zador D, Evers R, Groshkova T, Charles V, Martin A, Forzisi L. Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet. 2010;375:1885–1895. [PubMed] [Google Scholar]

196. Ross S, Peselow E. Pharmacotherapy of addictive disorders. Clin Neuropharmacol. 2009;32:277–289. [PubMed] [Google Scholar]

197. O’Brien CP. Anticraving medications for relapse prevention: a possible new class of psychoactive medications. Am J Psychiatry. 2005;162:1423–1431. [PubMed] [Google Scholar]

198. Ray LA, Chin PF, Miotto K. Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets. 2010;9:13–22. [PubMed] [Google Scholar]

199. Altshuler HL, Phillips PA, Feinhandler DA. Alteration of ethanol self-administration by naltrexone. Life Sci. 1980;26:679–688. [PubMed] [Google Scholar]

200. Gonzales RA, Weiss F. Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. J Neurosci. 1998;18:10663–10671. [PMC free article] [PubMed] [Google Scholar]

201. Roberts AJ, McDonald JS, Heyser CJ, Kieffer BL, Matthes HWD, Koob GF, Gold LH. μ-Opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther. 2000;293:1002–1008. [PubMed] [Google Scholar]

202. Gardner EL, Paredes W, Smith D, Zukin RS. Facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol is mediated by an endogenous opioid mechanism. Adv Biosci. 1989;75:671–674. [Google Scholar]

203. Chen J, Paredes W, Li J, Smith D, Lowinson J, Gardner EL. Δ9-Tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology. 1990;102:156–162. [PubMed] [Google Scholar]

204. Tanda G, Pontieri FE, Di Chiara G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common μ1 opioid receptor mechanism. Science. 1997;276:2048–2050. [PubMed] [Google Scholar]

205. Mason BJ, Heyser CJ. Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence. CNS Neurol Disord Drug Targets. 2010;9:23–32. [PMC free article] [PubMed] [Google Scholar]

206. Ameisen O. Complete and prolonged suppression of symptoms and consequences of alcohol-dependence using high-dose baclofen: a self-case report of a physician. Alcohol Alcohol. 2005;40:147–150. [PubMed] [Google Scholar]

207. Ameisen O. The End of My Addiction. New York: Farrar, Straus and Giroux; 2008. [Google Scholar]

208. Addolorato G, Leggio L. Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des. 2010;16:2113–2117. [PubMed] [Google Scholar]

209. Mason BJ, Heyser CJ. The neurobiology, clinical efficacy and safety of acamprosate in the treatment of alcohol dependence. Expert Opin Drug Saf. 2010;9:177–188. [PubMed] [Google Scholar]

210. Roberts DCS, Andrews MM, Vickers GJ. Baclofen attenuates the reinforcing effects of cocaine in rats. Neuropsychopharmacology. 1996;15:417–423. [PubMed] [Google Scholar]

211. Roberts DCS, Andrews MM. Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure. Psychopharmacology. 1997;131:271–277. [PubMed] [Google Scholar]

212. Brebner K, Phelan R, Roberts DCS. Intra-VTA baclofen attenuates cocaine self-administration on a progressive ratio schedule of reinforcement. Pharmacol Biochem Behav. 2000;66:857–862. [PubMed] [Google Scholar]

213. Brebner K, Phelan R, Roberts DCS. Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules. Psychopharmacology. 2000;148:314–321. [PubMed] [Google Scholar]

214. Roberts DCS, Brebner K. GABA modulation of cocaine self-administration. Ann NY Acad Sci. 2000;909:145–158. [PubMed] [Google Scholar]

215. Cousins MS, Roberts DCS, de Wit H. GABAB receptor agonists for the treatment of drug addiction: a review of recent findings. Drug Alcohol Depend. 2002;65:209–220. [PubMed] [Google Scholar]

216. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296:56–63. [PubMed] [Google Scholar]

217. Garrison GD, Dugan SE. Varenicline: a first-line treatment option for smoking cessation. Clin Ther. 2009;31:463–491. [PubMed] [Google Scholar]

218. Spiller K, Xi ZX, Li X, Ashby CR, Jr, Callahan PM, Tehim A, Gardner EL. Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of α4β2 nicotinic receptors in rats. Neuropharmacology. 2009;57:60–66. [PMC free article] [PubMed] [Google Scholar]

219. Glynn DA, Cryan JF, Kent P, Flynn RA, Kennedy MP. Update on smoking cessation therapies. Adv Ther. 2009;26:369–382. [PubMed] [Google Scholar]

220. Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S. Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology. 2002;163:102–105. [PubMed] [Google Scholar]

221. Semmer JE, Martin BR, Damaj MI. Bupropion is a nicotinic antagonist. J Pharmacol Exp Ther. 2000;295:321–327. [PubMed] [Google Scholar]

222. Froimowitz M, Wu KM, Moussa A, Haidar RM, Jurayj J, George C, Gardner EL. Slow-onset, long-duration 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake blockers as potential medications to treat cocaine abuse. J Med Chem. 2000;43:4981–4992. [PubMed] [Google Scholar]

223. Desai RI, Kopajtic TA, Koffarnus M, Newman AH, Katz JL. Identification of a dopamine transporter ligand that blocks the stimulant effects of cocaine. J Neurosci. 2005;25:1889–1893. [PMC free article] [PubMed] [Google Scholar]

224. Gardner EL, Liu X, Paredes W, Giordano A, Spector J, Lepore M, Wu KM, Froimowitz M. A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: effects in laboratory rat models relating to addiction. Neuropharmacology. 2006;51:993–1003. [PubMed] [Google Scholar]

225. Tanda G, Newman AH, Katz JL. Discovery of drugs to treat cocaine dependence: behavioral and neurochemical effects of atypical dopamine transport inhibitors. Adv Pharmacol. 2009;57:253–289. [PMC free article] [PubMed] [Google Scholar]

226. Peng X-Q, Xi Z-X, Li X, Spiller K, Li J, Chun L, Wu K-M, Froimowitz M, Gardner EL. Is slow-onset long-acting monoamine transport blockade to cocaine as methadone is to heroin? Implication for anti-addiction medications. Neuropsychopharmacology. 2010 in press [Epub ahead of print 08 Sept 2010] [PMC free article] [PubMed] [Google Scholar]

227. Carlezon WA, Jr, Wise RA. Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex. J Neurosci. 1996;16:3112–3122. [PMC free article] [PubMed] [Google Scholar]

228. Kushner SA, Dewey SL, Kornetsky C. Gamma-vinyl GABA attenuates cocaine-induced lowering of brain stimulation reward thresholds. Psychopharmacology. 1997;133:383–388. [PubMed] [Google Scholar]

229. Dewey SL, Morgan AE, Ashby CR, Jr, Horan B, Kushner SA, Logan J, Volkow ND, Fowler JS, Gardner EL, Brodie JD. A novel strategy for the treatment of cocaine addiction. Synapse. 1998;30:119–129. [PubMed] [Google Scholar]

230. Dewey SL, Brodie JD, Gerasimov M, Horan B, Gardner EL, Ashby CR., Jr A pharmacologic strategy for the treatment of nicotine addiction. Synapse. 1999;31:76–86. [PubMed] [Google Scholar]

231. Kushner SA, Dewey SL, Kornetsky C. The irreversible γ-aminobutyric acid (GABA) transaminase inhibitor γ-vinyl-GABA blocks cocaine self-administration in rats. J Pharmacol Exp Ther. 1999;290:797–802. [PubMed] [Google Scholar]

232. Gerasimov MR, Ashby CR, Jr, Gardner EL, Mills MJ, Brodie JD, Dewey SL. Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine. Synapse. 1999;34:11–19. [PubMed] [Google Scholar]

233. Paul M, Dewey SL, Gardner EL, Brodie JD, Ashby CR., Jr Gamma-vinyl GABA (GVG) blocks expression of the conditioned place preference response to heroin in rats. Synapse. 2001;41:219–220. [PubMed] [Google Scholar]

234. Gardner EL, Schiffer WK, Horan BA, Highfield D, Dewey SL, Brodie JD, Ashby CR., Jr Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats. Synapse. 2002;46:240–250. [PubMed] [Google Scholar]

235. Brodie JD, Figueroa E, Dewey SL. Treating cocaine addiction: from preclinical to clinical trial experience with gamma-vinyl GABA. Synapse. 2003;50:261–265. [PubMed] [Google Scholar]

236. Peng X-Q, Li X, Gilbert JG, Pak AC, Ashby CR, Jr, Brodie JD, Dewey SL, Gardner EL, Xi Z-X. Gamma-vinyl GABA inhibits cocaine-triggered reinstatement of drug-seeking behavior in rats by a non-dopaminergic mechanism. Drug Alcohol Depend. 2008;97:216–225. [PMC free article] [PubMed] [Google Scholar]

237. DeMarco A, Dalal RM, Pai J, Aquilina SD, Mullapudi U, Hammel C, Kothari SK, Kahanda M, Liebling CN, Patel V, Schiffer WK, Brodie JD, Dewey SL. Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference. Synapse. 2009;63:87–94. [PMC free article] [PubMed] [Google Scholar]

238. Brodie JD, Case BG, Figueroa E, Dewey SL, Robinson JA, Wanderling JA, Laska EM. Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees. Am J Psychiatry. 2009;166:1269–1277. [PubMed] [Google Scholar]

239. Gardner EL, Paredes W, Smith D, Donner A, Milling C, Cohen D, Morrison D. Facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol. Psychopharmacology. 1988;96:142–144. [PubMed] [Google Scholar]

240. Gardner EL, Lowinson JH. Marijuana's interaction with brain reward systems: update 1991. Pharmacol Biochem Behav. 1991;40:571–580. [PubMed] [Google Scholar]

241. Lepore M, Vorel SR, Lowinson J, Gardner EL. Conditioned place preference induced by Δ9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci. 1995;56:2073–2080. [PubMed] [Google Scholar]

242. De Vries TJ, Homberg JR, Binnekade R, Raasø H, Schoffelmeer ANM. Cannabinoid modulation of the reinforcing and motivational properties of heroin and heroin-associated cues in rats. Psychopharmacology. 2003;168:164–169. [PubMed] [Google Scholar]

243. Fattore L, Spano MS, Cossu G, Deiana S, Fratta W. Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats. Eur J Neurosci. 2003;17:1723–1726. [PubMed] [Google Scholar]

244. Anggadiredja K, Nakamichi M, Hiranita T, Tanaka H, Shoyama Y, Watanabe S, Yamamoto T. Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade. Neuropsychopharmacology. 2004;29:1470–1478. [PubMed] [Google Scholar]

245. Spano MS, Fattore L, Cossu G, Deiana S, Fadda P, Fratta W. CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat. Br J Pharmacol. 2004;143:343–350. [PMC free article] [PubMed] [Google Scholar]

246. Yamamoto T, Anggadiredja K, Hiranita T. New perspectives in the studies on endocannabinoid and cannabis: a role for the endocannabinoid-arachidonic acid pathway in drug reward and long-lasting relapse to drug taking. J Pharmacol Sci. 2004;96:382–388. [PubMed] [Google Scholar]

247. Gardner EL. Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav. 2005b;81:263–284. [PubMed] [Google Scholar]

248. Fattore L, Spano S, Cossu G, Deiana S, Fadda P, Fratta W. Cannabinoid CB1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats. Neuropharmacology. 2005;48:1097–1104. [PubMed] [Google Scholar]

249. Le Foll B, Goldberg SR. Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther. 2005;312:875–883. [PubMed] [Google Scholar]

250. Economidou D, Mattioli L, Cifani C, Perfumi M, Massi M, Cuomo V, Trabace L, Ciccocioppo R. Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats. Psychopharmacology. 2006;183:394–403. [PubMed] [Google Scholar]

251. fa*gerström K, Balfour DJ. Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Exp Opin Investig Drugs. 2006;15:107–116. [PubMed] [Google Scholar]

252. Li X, Hoffman AF, Peng X-Q, Lupica CR, Gardner EL, Xi Z-X. Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice. Psychopharmacology. 2009;204:1–11. [PMC free article] [PubMed] [Google Scholar]

253. Uys JD, LaLumiere RT. Glutamate: the new frontier in pharmacotherapy for cocaine addiction. CNS Neurol Disord Drug Targets. 2008;7:482–491. [PubMed] [Google Scholar]

254. Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10:561–572. [PubMed] [Google Scholar]

255. Kalivas PW, Lalumiere RT, Knackstedt L, Shen H. Glutamate transmission in addiction. Neuropharmacology. 2009;56(suppl.1):169–173. [PMC free article] [PubMed] [Google Scholar]

256. Knackstedt LA, Kalivas PW. Glutamate and reinstatement. Curr Opin Pharmacol. 2009;9:59–64. [PMC free article] [PubMed] [Google Scholar]

257. Olive MF. Metabotropic glutamate receptor ligands as potential therapeutics for addiction. Curr Drug Abuse Rev. 2009;2:83–98. [PMC free article] [PubMed] [Google Scholar]

258. Moussawi K, Kalivas PW. Group II metabotropic glutamate receptors (mGlu2/3) in drug addiction. Eur J Pharmacol. 2010;639:115–122. [PMC free article] [PubMed] [Google Scholar]

259. Schmidt HD, Pierce RC. Cocaine-induced neuroadaptations in glutamate transmission: potential therapeutic targets for craving and addiction. Ann NY Acad Sci. 2010;1187:35–75. [PMC free article] [PubMed] [Google Scholar]

260. Wise RA, Morales M. A ventral tegmental CRF-glutamate-dopamine interaction in addiction. Brain Res. 2010;1314:38–43. [PMC free article] [PubMed] [Google Scholar]

261. Li X, Gardner EL, Xi Z-X. The metabotropic glutamate receptor 7 (mGluR7) allosteric agonist AMN082 modulates nucleus accumbens GABA and glutamate, but not dopamine, in rats. Neuropharmacology. 2008;54:542–551. [PMC free article] [PubMed] [Google Scholar]

262. Li X, Li J, Gardner EL, Xi Z-X. Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats. J Neurochem. 2010;114:1368–1380. [PMC free article] [PubMed] [Google Scholar]

263. Peng X-Q, Li J, Gardner EL, Ashby CR, Jr, Thomas A, Wozniak K, Slusher BS, Xi Z-X. Oral administration of the NAALADase inhibitor GPI-5693 attenuates cocaine-induced reinstatement of drug-seeking behavior in rats. Eur J Pharmacol. 2010;627:156–161. [PMC free article] [PubMed] [Google Scholar]

264. Xi Z-X, Kiyatkin M, Li X, Peng X-Q, Wiggins A, Spiller K, Li J, Gardner EL. N-acetyl-aspartatylglutamate (NAAG) attenuates cocaine-enhanced brain-stimulation reward and cocaine self-administration in rats. Neuropharmacology. 2010;58:304–313. [PMC free article] [PubMed] [Google Scholar]

265. Xi Z-X, Li X, Peng X-Q, Li J, Chun L, Gardner EL, Thomas AG, Slusher BS, Ashby CR., Jr Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism. J Neurochem. 2010;112:564–576. [PMC free article] [PubMed] [Google Scholar]

266. Valdez GR, Koob GF. Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y systems: implications for the development of alcoholism. Pharmacol Biochem Behav. 2004;79:671–689. [PubMed] [Google Scholar]

267. Funk CK, O'Dell LE, Crawford EF, Koob GF. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci. 2006;26:11324–11332. [PMC free article] [PubMed] [Google Scholar]

268. Chu K, Koob GF, Cole M, Zorrilla EP, Roberts AJ. Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF1 receptor antagonist antalarmin and by CRF1 receptor knockout. Pharmacol Biochem Behav. 2007;86:813–821. [PMC free article] [PubMed] [Google Scholar]

269. Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol Psychiatry. 2007;61:78–86. [PMC free article] [PubMed] [Google Scholar]

270. George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O'Dell LE, Richardson HN, Koob GF. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc Natl Acad Sci USA. 2007;104:17198–171203. [PMC free article] [PubMed] [Google Scholar]

271. Gilpin NW, Richardson HN, Koob GF. Effects of CRF1 -receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats. Alcohol Clin Exp Res. 2008;32:1535–1542. [PMC free article] [PubMed] [Google Scholar]

272. Ji D, Gilpin NW, Richardson HN, Rivier CL, Koob GF. Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats. Behav Pharmacol. 2008;19:1–12. [PMC free article] [PubMed] [Google Scholar]

273. Papaleo F, Ghozland S, Ingallinesi M, Roberts AJ, Koob GF, Contarino A. Disruption of the CRF2 receptor pathway decreases the somatic expression of opiate withdrawal. Neuropsychopharmacology. 2008;33:2878–2887. [PMC free article] [PubMed] [Google Scholar]

274. Specio SE, Wee S, O'Dell LE, Boutrel B, Zorrilla EP, Koob GF. CRF1 receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology. 2008;96:473–482. [PMC free article] [PubMed] [Google Scholar]

275. Greenwell TN, Funk CK, Cottone P, Richardson HN, Chen SA, Rice KC, Zorrilla EP, Koob GF. Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats. Addict Biol. 2009;14:130–143. [PMC free article] [PubMed] [Google Scholar]

276. Koob GF. Brain stress systems in the amygdala and addiction. Brain Res. 2009;1293:61–75. [PMC free article] [PubMed] [Google Scholar]

277. Koob GF. The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res. 2010;1314:3–14. [PMC free article] [PubMed] [Google Scholar]

278. Zorrilla EP, Koob GF. Progress in corticotropin-releasing factor-1 antagonist development. Drug Discov Today. 2010;5:371–383. [PMC free article] [PubMed] [Google Scholar]

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