Development of pharmacotherapies for drug addiction: A Rosetta stone approach

Nature Reviews Drug Discovery

Volumn 8, Issue 6, 2009, Pages 500-515

  Koob, George F ^a   Kenneth Lloyd, G ^b   Mason, Barbara J ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b Nereus Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (6 DIMETHYLAMINO 4 METHYL 3 PYRIDINYL) 7 DIPROPYLAMINO 2,5 DIMETHYLPYRAZOLO[1,5 A]PYRIMIDINE; 4 AMINOBUTYRIC ACID A RECEPTOR BLOCKING AGENT; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; 4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; ACAMPROSATE; AMFEBUTAMONE; BACLOFEN; BUPRENORPHINE; BUPRENORPHINE PLUS NALOXONE; CORTICOTROPIN RELEASING FACTOR ANTAGONIST; CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 ANTAGONIST; CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 ANTAGONIST; CP 316311; DISULFIRAM; DOPAMINE 1 RECEPTOR BLOCKING AGENT; DOPAMINE 3 RECEPTOR BLOCKING AGENT; DYNORPHIN ANTAGONIST; GABAPENTIN; KAPPA OPIATE RECEPTOR ANTAGONIST; METHADONE; MU OPIATE RECEPTOR ANTAGONIST; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NALTREXONE; NICOTINE; PLACEBO; PRAZOSIN; SERTRALINE; TOPIRAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARENICLINE;

ALCOHOL WITHDRAWAL; ALCOHOLISM; ANXIETY DISORDER; BEHAVIOR THERAPY; CLINICAL TRIAL; COCAINE DEPENDENCE; DEPRESSION; DISEASE ACTIVITY; DOPAMINERGIC SYSTEM; DRINKING BEHAVIOR; DRUG ALCOHOL INTERACTION; DRUG BIOAVAILABILITY; DRUG DEPENDENCE; DRUG DEPENDENCE TREATMENT; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG SCREENING; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; GENETIC VARIABILITY; HEROIN DEPENDENCE; HUMAN; INTRAVENOUS DRUG ABUSE; LOW DRUG DOSE; MULTIPLE SCLEROSIS; NEUROMODULATION; NEUROPATHOLOGY; NEUROPHARMACOLOGY; NEUROTRANSMITTER RELEASE; NONHUMAN; OPIATE ADDICTION; PATIENT ATTITUDE; PHARMACOGENETICS; PRIORITY JOURNAL; PRODUCT DEVELOPMENT; RECURRENT DISEASE; REVIEW; SIDE EFFECT; SMOKING CESSATION; STAGING; SUBSTANCE ABUSE; TOBACCO DEPENDENCE; TRANSDERMAL PATCH; WITHDRAWAL SYNDROME;

ANIMALS; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; NERVE NET; PHARMACEUTICAL PREPARATIONS; SUBSTANCE-RELATED DISORDERS;

EID: 66749168712     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2828     Document Type: Review

References (209)

1. Koob, G. F. & Le Moal, M. Drug abuse: Hedonic homeostatic dysregulation. Science 278, 52-58 (1997).
2. Kreek, M. J., LaForge, K. S. & Butelman, E. Pharmacotherapy of addictions. Nature Rev. Drug Discov. 1, 710-726 (2002); erratum 1, 926 (2002).
3. Deroche-Gamonet, V., Belin, D. & Piazza, P. V. Evidence for addiction-like behavior in the rat. Science 305, 1014-1017 (2004).
4. Vanderschuren, L. J. & Everitt, B. J. Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305, 1017-1019 (2004).
5. Heinz, A., Beck, A., Grüsser, S. M., Grace, A. A. & Wrase, J. Identifying the neural circuitry of alcohol craving and relapse vulnerability. Addict. Biol. 14, 108-118 (2009).
6. Sanchis-Segura, C. & Spanagel, R. Behavioural assessment of drug reinforcement and addictive features in rodents: An overview. Addict. Biol. 11, 2-38 (2006).
7. Koob, G. F. & Le Moal, M. Neurobiology of Addiction Elsevier, London, 2006).
8. Nestler, E. J. Is there a common molecular pathway for addiction? Nature Neurosci. 8, 1445-1449 (2005).
9. Kalivas, P. W. & McFarland, K. Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 168, 44-56 (2003).
10. Vanderschuren, L. J. & Everitt, B. J. Behavioral and neural mechanisms of compulsive drug seeking. Eur. J. Pharmacol. 526, 77-88 (2005).
11. Koob, G. F. & Le Moal, M. Plasticity of reward neurocircuitry and the 'dark side' of drug addiction. Nature Neurosci. 8, 1442-1444 (2005).
12. Koob, G. F. & Le Moal, M. Addiction and the brain antireward system. Annu. Rev. Psychol. 59, 29-53 (2008).
13. Koob, G. F. A role for brain stress systems in addiction. Neuron 59, 11-34 (2008).
14. Nestler, E. J. Molecular neurobiology of addiction. Am. J. Addict. 10, 201-217 (2001).
15. Shaham, Y., Shalev, U., Lu, L., de Wit, H. & Stewart, J. The reinstatement model of drug relapse: History, methodology and major findings. Psychopharmacology 168, 3-20 (2003).
16. Schultz, W. Multiple dopamine functions at different time courses. Annu. Rev. Neurosci. 30, 259-288 (2007).
17. Berridge, K. C. The debate over dopamine's role in reward: The case for incentive salience. Psychopharmacology 191, 391-431 (2007).
18. Weiss, F. & Koob, G. F. Drug addiction: Functional neurotoxicity of the brain reward systems. Neurotox. Res. 3, 145-156 (2000).
19. Weiss, F., Markou, A., Lorang, M. T. & Koob, G. F. Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res. 593, 314-318 (1992).
20. Weiss, F. et al. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J. Neurosci. 16 3474-3485 (1996).
21. Melis, M., Spiga, S. & Diana, M. The dopamine hypothesis of drug addiction: Hypodopaminergic state. Int. Rev. Neurobiol. 63, 101-154 (2005).
22. Pulvirenti, L. & Koob, G. F. Being partial to psychostimulant addiction therapy. Trends Pharmacol. Sci. 23, 151-153 (2002).
23. Clark, D. et al. Behavioural profile of partial D2 dopamine receptor agonists: 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy. Psychopharmacology 105 381-392 (1991).
24. Pulvirenti, L. & Koob, G. F. Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol. Sci. 15, 374-379 (1994).
25. Svensson, K. et al. Effects of the partial dopamine receptor agonists SDZ 208-911, SDZ 208-912 and terguride on central monoamine receptors: A behavioral, biochemical and electrophysiological study. Naunyn Schmiedebergs Arch. Pharmacol. 344, 263-274 (1991).
26. Pulvirenti, L., Smith, D. & Koob, G. F. SDZ 208-911, an amino-ergoline with partial dopamine agonistic properties, dose dependently increases cocaine self-administration in the rat. Psychopharmacology 113 518-520 (1994).
27. Pulvirenti, L., Balducci, C., Piercy, M. & Koob, G. F. Characterization of the effects of the partial dopamine agonist terguride on cocaine self-administration in the rat. J. Pharmacol. Exp. Ther. 286 1231-1238 (1998).
28. Izzo, E., Orsini, C., Koob, G. F. & Pulvirenti, L. A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule. Pharmacol. Biochem. Behav. 68, 701-708 (2001).
29. Bono, G., Balducci, C., Richelmi, P., Koob, G. F. & Pulvirenti, L. Dopamine partial receptor agonists reduce ethanol intake in the rat. Eur. J. Pharmacol. 296, 233-238 (1996).
30. Orsini, C., Koob, G. F. & Pulvirenti, L. Dopamine partial agonist reverses amphetamine withdrawal in rats. Neuropsychopharmacology 25, 789-792 (2001).
31. Hoefer, M. E., Voskanian, S. J., Koob, G. F. & Pulvirenti, L. Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat. Pharmacol. Biochem. Behav. 83, 403-409 (2006).
32. 2 receptor agonist, on increased rate of methamphetamine self-administration in rats with prolonged access. Neuropsychopharmacology 32, 2238-2247 (2007).
33. 3 receptors in drug addiction: A review of pharmacological evidence. Brain Res. Rev. 49, 77-105 (2005).
34. 3 receptor partial agonist in animal models of cocaine abuse. J. Pharmacol. Exp. Ther. 320, 1268-1278 (2007).
35. 3 receptor agonist. Nature 400, 371-375 (1999).
36. 3 receptor-preferring partial agonist BP 897 dose-dependently attenuates the expression of amphetamine-conditioned place preference in rats. Behav. Pharmacol. 16, 181-186 (2005).
37. Caine, S. B. & Koob, G. F. Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food. J. Exp. Anal. Behav. 61, 213-221 (1994).
38. Haile, C. N. & Kosten, T. A. Differential effects of D1- and D2-like compounds on cocaine self-administration in Lewis and Fischer 344 inbred rats. J. Pharmacol. Exp. Ther. 299, 509-518 (2001).
39. Spanagel, R. & Kiefer, F. Drugs for relapse prevention of alcoholism: ten years of progress. Trends Pharmacol. Sci. 29, 109-115 (2008).
40. Rassnick, S., D'Amico, E., Riley, E. & Koob, G. F. GABA antagonist and benzodiazepine partial inverse agonist reduce motivated responding for ethanol. Alcohol. Clin. Exp. Res. 17, 124-130 (1993).
41. A receptor antagonism in the extended amygdala decreases ethanol self-administration in rats. Eur. J. Pharmacol. 283, 151-159 (1995).
42. Weerts, E. M., Froestl, W. & Griffiths, R. R. Effects of GABAergic modulators on food and cocaine self-administration in baboons. Drug Alcohol Depend. 80, 369-376 (2005).
43. B receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats. J. Pharmacol. Exp. Ther. 326, 306-314 (2008).
44. Colombo, G. et al. Baclofen suppresses motivation to consume alcohol in rats. Psychopharmacology 167, 221-224 (2003).
45. Xi, Z. X. & Stein, E. A. Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release. J. Pharmacol. Exp. Ther. 290, 1369-1374 (1999).
46. Frye, G. D., McCown, T. J. & Breese, G. R. Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA) mimetics: Blockade of audiogenic seizures but not forelimb tremors. J. Pharmacol. Exp. Ther. 226, 720-725 (1983).
47. Addolorato, G. et al. Baclofen efficacy in reducing alcohol craving and intake: A preliminary double-blind randomized controlled study. Alcohol Alcohol. 37, 504-508 (2002).
48. Addolorato, G. et al. Rapid suppression of alcohol withdrawal syndrome by baclofen. Am. J. Med. 112, 226-229 (2002).
49. Walker, B. M. & Koob, G. F. The γ-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats. Alcohol. Clin. Exp. Res. 31, 11-18 (2007).
50. Ahmadi-Abhari, S. A. et al. Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: A double-blind randomized controlled trial. J. Clin. Pharmacol. Ther. 26, 67-71 (2001).
51. Sills, G. J. The mechanisms of action of gabapentin and pregabalin. Curr. Opin. Pharmacol. 6, 108-113 (2006).
52. Taylor, C. P. et al. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res. 29, 233-249 (1998).
53. Gotz, E., Feuerstein, T. J., Lais, A. & Meyer, D. K. Effects of gabapentin on release of gamma-aminobutyric acid from slices of rat neostriatum. Arzneimittelforschung 43, 636-638 (1993).
54. 2+ influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Brit. J. Pharmacol. 130, 900-906 (2000).
55. Bertrand, S. et al. The anticonvulsant, antihyperalgesic agent gabapentin is an agonist at brain γ-aminobutyric acid type B receptors negatively coupled to voltage-dependent calcium channels. J. Pharmacol. Exp. Ther. 298, 15-24 (2001).
56. Roberto, M. et al. Cellular and behavioral interactions of gabapentin with alcohol dependence. J. Neurosci. 28, 5762-5771 (2008).
57. Mason, B. J., Light, J. M., Williams, L. D. & Drobes, D. J. Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: Effects of gabapentin. Addict. Biol. 14, 73-83 (2009).
58. Koob, G. F., Heinrichs, S. C., Menzaghi, F., Pich, E. M. & Britton, K. T. Corticotropin releasing factor, stress and behavior. Semin. Neurosci. 6, 221-229 (1994).
59. Swanson, L. W., Sawchenko, P. E., Rivier, J. & Vale, W. The organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: An immunohistochemical study. Neuroendocrinology 36, 165-186 (1983).
60. Sarnyai, Z. et al. Brain corticotropin-releasing factor mediates "anxiety-like" behavior induced by cocaine withdrawal in rats. Brain Res. 675, 89-97 (1995).
61. Basso, A. M., Spina, M., Rivier, J., Vale, W. & Koob, G. F. Corticotropin-releasing factor antagonist attenuates the "anxiogenic-like" effect in the defensive burying paradigm but not in the elevated plus-maze following chronic cocaine in rats. Psychopharmacology 145, 21-30 (1999).
62. Knapp, D. J., Overstreet, D. H., Moy, S. S. & Breese, G. R. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats. Alcohol 32, 101-111 (2004).
63. Overstreet, D. H., Knapp, D. J. & Breese, G. R. Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors. Pharmacol. Biochem. Behav. 77, 405-413 (2004).
64. 1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc. Natl Acad. Sci. USA 104, 17198-17203 (2007).
65. Stinus, L., Cador, M., Zorrilla, E. P. & Koob, G. F. Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. Neuropsychopharmacology 30 90-98 (2005).
66. Rodriguez de Fonseca, F., Carrera, M. R. A., Navarro, M., Koob, G. F. & Weiss, F. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science, 276, 2050-2054 (1997).
67. Funk, C. K., O'Dell, L. E., Crawford, E. F. & Koob, G. F. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J. Neurosci. 26, 11324-11332 (2006).
68. Merlo-Pich, E. et al. Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J. Neurosci. 15, 5439-5447 (1995).
69. Olive, M. F., Koenig, H. N., Nannini, M. A. & Hodge, C. W. Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake. Pharmacol. Biochem. Behav. 72, 213-220 (2002).
70. Richter, R. M. & Weiss, F. In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 32, 254-261 (1999).
71. Weiss, F. et al. Compulsive drug-seeking behavior and relapse: neuroadaptation, stress, and conditioning factors. Ann. NY Acad. Sci. 937, 1-26 (2001).
72. Baldwin, H. A., Rassnick, S., Rivier, J., Koob, G. F. & Britton, K. T. CRF antagonist reverses the "anxiogenic" response to ethanol withdrawal in the rat. Psychopharmacology 103, 227-232 (1991).
73. Valdez, G. R. et al. Increased ethanol self-administration and anxiety-like behavior during acute withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol. Clin. Exp. Res. 26, 1494-1501 (2002).
74. Gehlert, D. R. et al. 3-(4-chloro-2-morpholin-4-yl-thiaz ol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo(1,2-b) pyridazine: A novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. J. Neurosci. 27, 2718-2726 (2007).
75. Funk, C. K., Zorrilla, E. P., Lee, M. J., Rice, K. C. & Koob, G. F. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol. Psychol. 61, 78-86 (2007).
76. 1 receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology 196, 473-482 (2008).
77. Greenwell, T. N. et al. Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long-, but not short-access rats. Addict. Biol. 14, 130-143 (2009).
78. Zobel, A. W. et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: The first 20 patients treated. J. Psychiatr. Res. 34, 171-181 (2000).
79. Binneman, B. et al. A 6-week randomized, placebo-controlled trial of CP-316311 (a selective CRH1 antagonist) in the treatment of major depression. Am. J. Psychiatry 165, 617-620 (2008).
80. 1-Noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol 42, 91-97 (2008).
81. 1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration. Pharmacol. Biochem. Behav. 91, 295-302 (2009).
82. 1-Noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access. Eur. Neuropsychopharmacol. 18, 303-311 (2008).
83. Shippenberg, T. S., Zapata, A. & Chefer, V. I. Dynorphin and the pathophysiology of drug addiction. Pharmacol. Ther. 116, 306-321 (2007).
84. Mucha, R. F. & Herz, A. Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology 86, 274-280 (1985).
85. Pfeiffer, A., Brantl, V., Herz, A. & Emrich, H. M. Psychotomimesis mediated by kappa opiate receptors. Science 233, 774-776 (1986).
86. Sivam, S. P. Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. J. Pharmacol. Exp. Ther. 250, 818-824 (1989).
87. Spangler, R., Unterwald, E. M. & Kreek, M. J. "Binge" cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen. Mol. Brain Res. 19, 323-327 (1993).
88. Hurd, Y. L. & Herkenham, M. Molecular alterations in the neostriatum of human cocaine addicts. Synapse 13, 357-369 (1993).
89. Unterwald, E. M., Rubenfeld, J. M. & Kreek, M. J. Repeated cocaine administration upregulates kappa and mu, but not delta, opioid receptors. Neuroreport 5, 1613-1616 (1994).
90. Nestler, E. J. Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol. Sci. 25, 210-218 (2004).
91. Shirayama, Y. et al. Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. J. Neurochem. 90, 1258-1268 (2004).
92. Land, B. B. et al. The dysphoric component of stress is encoded by activation of the dynorphin κ-opioid system. J. Neurosci. 28 407-414 (2008).
93. McLaughlin, J. P., Marton-Popovici, M. & Chavkin, C. Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J. Neurosci. 23, 5674-5683 (2003).
94. Beardsley, P. M., Howard, J. L., Shelton, K. L. & Carroll, F. I. Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats. Psychopharmacology 183, 118-126 (2005).
95. Valdez, G. R., Platt, D. M., Rowlett, J. K., Rüedi-Bettschen, D. & Spealman, R. D. Kappa agonist-induced reinstatement of cocaine seeking in squirrel monkeys: A role for opioid and stress-related mechanisms. J. Pharmacol. Exp. Ther. 323, 525-533 (2007).
96. Negus, S. S. et al. Effect of antagonists selective for mu, delta and kappa opioid receptors on the reinforcing effects of heroin in rats. J. Pharmacol. Exp. Ther. 265, 1245-1252 (1993).
97. Walker, B. M. & Koob, G. F. Pharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence. Neuropsychopharmacology 33, 643-652 (2008).
98. Heilig, M., Koob, G. F., Ekman, R. & Britton, K. T. Corticotropin-releasing factor and neuropeptide Y: Role in emotional integration. Trends Neurosci. 17, 80-85 (1994).
99. Ciccocioppo, R., Angeletti, S., Panocka, I. & Massi, M. Nociceptin-orphanin FQ and drugs of abuse. Peptides 21, 1071-1080 (2000).
100. George, D. T. et al. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science 319, 1536-1539 (2008).
101. Hoffman, P. L., Rabe, C. S., Moses, F. & Tabakoff, B. N methyl-D-aspartate receptors and ethanol: Inhibition of calcium flux and cyclic GMP production. J. Neurochem. 52, 1937-1940 (1989).
102. de Witte, P., Littleton, J., Parot, P. & Koob, G. Neuroprotective and abstinence-promoting effects of acamprosate: Elucidating the mechanism of action. CNS Drugs 19, 517-537 (2005).
103. Littleton, J. M. Acamprosate in alcohol dependence: Implications of a unique mechanism of action. J. Addict. Med. 1, 115-125 (2007).
104. Li, Y., Vartanian, A. J., White, F. J., Xue, C. J. & Wolf, M. E. Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine. Psychopharmacology 134, 266-276 (1997).
105. Ungless, M. A., Whistler, J. L., Malenka, R. C. & Bonci, A. Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411, 583-387 (2001).
106. Conrad, K. L. et al. Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature 454 118-121 (2008).
107. Kalivas, P. W. et al. Glutamate transmission and addiction to cocaine. Ann. NY Acad. Sci. 1003, 169-175 (2003).
108. Everitt, B. J. & Wolf, M. E. Psychomotor stimulant addiction: A neural systems perspective. J. Neurosci. 22, 3312-3320 (2002); erratum 22, 1a (2002).
109. Vorel, S. R., Liu, X., Hayes, R. J., Spector, J. A. & Gardner, E. L. Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292, 1175-1178 (2001).
110. Engblom, D. et al. Glutamate receptors on dopamine neurons control the persistence of cocaine seeking. Neuron 59, 497-508 (2008).
111. Stringer, S., Rueve, M. & Mossman, D. Topiramate as treatment for alcohol dependence. J. Am. Med. Assoc. 299, 405-406 (2008).
112. Olmsted, C. L. & Kockler, D. R. Topiramate for alcohol dependence. Ann. Pharmacother. 42, 1475-1480 (2008).
113. Gabriel, K. I. & Cunningham, C. L. Effects of topiramate on ethanol and saccharin consumption and preferences in C57BL/6J mice. Alcohol. Clin. Exp. Res. 29, 75-80 (2005).
114. Farook, J. M., Lewis, B., Littleton, J. M. & Barron, S. Topiramate attenuates the stress-induced increase in alcohol consumption and preference in male C57BL/6J mice. Physiol. Behav. 96, 189-193 (2009).
115. Gremel, C. M., Gabriel, K. I. & Cunningham, C. L. Topiramate does not affect the acquisition or expression of ethanol conditioned place preference in DBA/2J or C57BL/6J mice. Alcohol. Clin. Exp. Res. 30, 783-790 (2006).
116. Di Ciano, P. & Everitt, B. J. Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior. Neuropsychopharmacology 25, 341-360 (2001).
117. Zhao, Y. et al. Activation of group II metabotropic glutamate receptors attenuates both stress and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus and amygdala. J. Neurosci. 26, 9967-9974 (2006).
118. 1/2 phosphorylation in specific limbic brain regions: Blockade by the mGluR5 antagonist MPEP. Neuropharmacology 55, 546-554 (2008).
119. Backstrom, P. & Hyytia, P. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology 31, 778-786 (2006).
120. Haney, M. Self-administration of cocaine, cannabis and heroin in the human laboratory: Benefits and pitfalls. Addict. Biol. 14, 9-21 (2009).
121. Mello, N. K., Mendelson, J. H., Kuehnle, J. C. & Sellers, M. S. Operant analysis of human heroin self-administration and the effects of naltrexone. J. Pharmacol. Exp. Ther. 216, 45-54 (1981).
122. Comer, S. D., Collins, E. D. & Fischman, M. W. Choice between money and intranasal heroin in morphine-maintained humans. Behav. Pharmacol. 8, 677-690 (1997).
123. Vocci, F. J. & Elkashef, A. Pharmacotherapy and other treatments for cocaine abuse and dependence. Curr. Opin. Psychiatry 18, 265-270 (2005).
124. Logan, G. D. in Inhibitory Processes in Attention, Memory and Language (eds Dagenbach, D. & Carr, T. H.) 189-236 (Academic Press, San Diego, 1994).
125. Dole, V. P. Implications of methadone maintenance for theories of narcotic addiction. J. Am. Med. Assoc. 260, 3025-3029 (1988).
126. Haney, M. et al. Marijuana withdrawal in humans: Effects of oral THC or divalproex. Neuropsychopharmacology 29, 158-170 (2004).
127. Evans, D. E. & Drobes, D. J. Nicotine self-medication of cognitive-attentional processing. Addict. Biol. 14, 32-42 (2009).
128. Kassel, J. D. & Unrod, M. Smoking, anxiety, and attention: Support for the role of nicotine in attentionally mediated anxiolysis. J. Abnorm. Psychol. 109, 161-166 (2000).
129. Koob, G. F. & Kreek, M. J. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am. J. Psychiatry 164, 1149-1159 (2007).
130. Drobes, D. J., Anton, R. F., Thomas, S. E. & Voronin, K. A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: Naltrexone and nalmefene. Neuropsychopharmacology 28, 755-764 (2003).
131. Krishnan-Sarin, S., Krystal, J. H., Shi, J., Pittman, B. & O'Malley, S. S. Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking. Biol. Psychiatry 62, 694-697 (2007).
132. Chornock, W. M., Stitzer, M. L., Gross, J. & Leischow, S. Experimental model of smoking re-exposure: Effects on relapse. Psychopharmacology 108, 495-500 (1992).
133. Carter, B. L. & Tiffany, S. T. Meta-analysis of cue-reactivity in addiction research. Addiction 94, 327-340 (1999).
134. Monti, P. M. et al. Naltrexone's effect on cue-elicited craving among alcoholics in treatment. Alcohol. Clin. Exp. Res. 23, 1386-1394 (1999).
135. Cooney, N. L., Litt, M. D., Morse, P. A., Bauer, L. O. & Gaupp, L. Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men. J. Abnorm. Psychol. 106, 243-250 (1997).
136. Miranda, R. Jr et al. Effects of topiramate on urge to drink and the subjective effects of alcohol: A preliminary laboratory study. Alcohol. Clin. Exp. Res. 32, 489-497 (2008).
137. Shiffman, S. et al. Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology 166, 343-350 (2003).
138. Hersh, D., Bauer, L. O. & Kranzler, H. R. Carbamazepine and cocaine-cue reactivity. Drug Alcohol Depend. 39, 213-221 (1995).
139. Robbins, S. J., Ehrman, R. N., Childress, A. R. & O'Brien, C. P. Using cue reactivity to screen medications for cocaine abuse: A test of amantadine hydrochloride. Addict. Behav. 17, 491-499 (1992).
140. Marlatt, G. & Gordon, J. in Behavioral Medicine: Changing Health Lifestyles (eds Davidson, P. & Davidson, S.) 410-452 (Brunner/Mazel, New York, 1980).
141. Childress, A. R. et al. Can induced moods trigger drug-related responses in opiate abuse patients? J. Subst. Abuse Treat. 11 17-23 (1994).
142. Sinha, R., Fuse, T., Aubin, L. R. & O'Malley, S. S. Psychological stress, drug-related cues and cocaine craving. Psychopharmacology 152, 140-148 (2000).
143. Lang, P. J., Kozak, M. J., Miller, G. A., Levin, D. N. & McLean, A. Jr. Emotional imagery: Conceptual structure and pattern of somato-visceral response. Psychophysiology 17, 179-192 (1980).
144. Fox, H. C., Bergquist, K. L., Hong, K. I. & Sinha, R. Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals. Alcohol. Clin. Exp. Res. 31, 395-403 (2007).
145. Sinha, R., Garcia, M., Paliwal, P., Kreek, M. J. & Rounsaville, B. J. Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch. Gen. Psychiatry 63, 324-331 (2006).
146. 1a-receptor agonist. Neuropsychopharmacology 30, 1662-1669 (2005).
147. al'Absi, M., Hatsukami, D. & Davis, G. L. Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse. Psychopharmacology 181, 107-117 (2005).
148. Sinha, R., Kimmerling, A., Doebrick, C. & Kosten, T. R. Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: Preliminary findings. Psychopharmacology 190 569-574 (2007).
149. Mason, B. J., Light, J. M., Escher, T. & Drobes, D. J. Effect of positive and negative affective stimuli and beverage cues on measures of craving in non treatment-seeking alcoholics. Psychopharmacology 200, 141-150 (2008).
150. McKee, S. A. Developing human laboratory models of smoking lapse behavior for medication screening. Addict. Biol. 14, 99-107 (2009).
151. Braus, D. F. et al. Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics. J. Neural Transm. 108 887-894 (2001).
152. Grusser, S. M. et al. Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology 175, 296-302 (2004).
153. Wrase, J. et al. Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. Neuroimage 35, 787-794 (2007).
154. Bond, C. et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: Possible implications for opiate addiction. Proc. Natl Acad. Sci. USA 95 9608-9613 (1998).
155. Treutlein, J. et al. Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples. Mol. Psychiatry 11, 594-602 (2006).
156. Garbutt, J. C. et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: A randomized controlled trial. J. Am. Med. Assoc. 293, 1617-1625 (2005); errata 293, 1978, 2864 (2005).
157. Huestis, M. A. & Cone, E. J. Differentiating new marijuana use from residual drug excretion in occasional marijuana users. J. Anal. Toxicol. 22, 445-454 (1998).
158. Sobell, L. C. & Sobell, M. B. in Measuring Alcohol Consumption: Psychosocial and Biochemical Methods (eds Litten, R. Z. & Allen, J. P.) 41-72 (Human Press, Totowa, 1992).
159. Office of National Drug Control Policy - The Economic Costs of Drug Abuse in the United States: 1992-2002. (Office of National Drug Control Policy, Washington DC, 2004).
160. National Institute on Alcohol Abuse and Alcoholism 10th special report to the US Congress on alcohol and health: Highlights from current research. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, 2000).
161. Centers for Disease Control and Prevention - annual smoking-attributable mortality, years of potential life lost, and productivity losses: United States, 1997-2001. Morb. Mort. Wkly Rep. 54, 625-628 (2005).
162. O'Brien, C. P. & McLellan, A. T. Myths about the treatment of addiction. Lancet 347, 237-240 (1996).
163. Lotsch, J. & Geisslinger, G. Are μ-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol. Med. 11, 82-89 (2005).
164. Ray, L. A. & Hutchison, K. E. A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans. Alcohol. Clin. Exp. Res. 28, 1789-1795 (2004).
165. Anton, R. F. et al. An evaluation of μ-opioid receptor (OPRM1 as a predictor of naltrexone response in the treatment of alcohol dependence: Results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch. Gen. Psychiatry 65, 135-144 (2008).
166. van der Zwaluw, C. S. et al. Polymorphisms in the μ-opioid receptor gene (OPRM1) and the implications for alcohol dependence in humans. Pharmacogenomics 8, 1427-1436 (2007).
167. Hernandez-Avila, C. A., Wand, G., Luo, X., Gelernter, J. & Kranzler, H. R. Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the mu-opioid receptor locus (OPRM1). Am. J. Med. Gen. B Neuropsych. Genet. 118B, 60-65 (2003).
168. Blomeyer, D. et al. Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol. Psychiatry 63, 146-151(2008).
169. Hansson, A. C. et al. Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc. Natl Acad. Sci. USA 103, 15236-15241 (2006).
170. Sommer, W. H. et al. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol. Psychiatry 63, 139-145 (2008).
171. Koob, G. F., Everitt, B. J. & Robbins, T. W. in Fundamental Neuroscience 3rd edn (eds Squire, L. G. et al.). 987-1016 (Academic Press, Amsterdam, 2008).
172. Collins, R. J., Weeks, J. R., Cooper, M. M., Good, P. I. & Russell, R. R. Prediction of abuse liability of drugs using IV self-administration by rats. Psychopharmacology 82, 6-13 (1984).
173. Kornetsky, C. & Bain, G. in Modern Methods in Pharmacology: Testing and Evaluation of Drugs of Abuse Vol. 6 (eds Adler, M. W. & Cowan, A.) 211-231 (Wiley-Liss, New York, 1990).
174. Tornatzky, W. & Miczek, K. A. Cocaine self-administration "binges": transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats. Psychopharmacology 148, 289-298 (2000).
175. Ahmed, S. H. & Koob, G. F. Transition from moderate to excessive drug intake: Change in hedonic set point. Science 282, 298-300 (1998).
176. 9-THC content? Exp. Clin. Psychopharmacol. 5, 74-82 (1997).
177. Haney, M., Foltin, R. W. & Fischman, M. W. Effects of pergolide on intravenous cocaine self-administration in men and women. Psychopharmacology 137, 15-24 (1998).
178. de Wit, H. Impulsivity as a determinant and consequence of drug use: A review of underlying processes. Addict. Biol. 14, 22-31 (2009).
179. Rachlin, H. & Green, L. Commitment, choice and self-control. J. Exp. Anal. Behav. 17, 15-22 (1972).
180. Leth-Steensen, C., Elbaz, Z. K. & Douglas, V. I. Mean response times, variability, and skew in the responding of ADHD children: A response time distributional approach. Acta Psychol. 104, 167-190 (2000).
181. Schulteis, G., Yackey, M., Risbrough, V. & Koob, G. F. Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze. Pharmacol. Biochem. Behav. 60, 727-731 (1998).
182. Tzschentke, T. M. Measuring reward with the conditioned place preference paradigm: A comprehensive review of drug effects, recent progress and new issues. Prog. Neurobiol. 56, 613-672 (1998).
183. Markou, A., Kosten, T. R. & Koob, G. F. Neurobiological similarities in depression and drug dependence: A self-medication hypothesis. Neuropsychopharmacology 18, 135-174 (1998).
184. Ahmed, S. H., Walker, J. R. & Koob, G. F. Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22, 413-421 (2000).
185. Roberts, A. J., Heyser, C. J., Cole, M., Griffin, P. & Koob, G. F. Excessive ethanol drinking following a history of dependence: Animal model of allostasis. Neuropsychopharmacology 22, 581-594 (2000).
186. Kitamura, O., Wee, S., Specio, S. E., Koob, G. F. & Pulvirenti, L. Escalation of methamphetamine self-administration in rats: A dose-effect function. Psychopharmacology 186, 48-53 (2006).
187. O'Dell, L. E. & Koob, G. F. "Nicotine deprivation effect" in rats with intermittent 23-hour access to intravenous nicotine self-administration. Pharmacol. Biochem. Behav. 86, 346-353 (2007).
188. Hjalmarson, A. I. Effect of nicotine chewing gum in smoking cessation: A randomized, placebo-controlled, double-blind study. J. Am. Med. Assoc. 252, 2835-2838 (1984).
189. Haney, M. The marijuana withdrawal syndrome: Diagnosis and treatment. Curr. Psychiatry Rep. 7, 360-366 (2005).
190. Rusted, J. M., Caulfield, D., King, L. & Goode, A. Moving out of the laboratory: Does nicotine improve everyday attention? Behav. Pharmacol. 11, 621-629 (2000).
191. Lawrence, N. S., Ross, T. J. & Stein, E. A. Cognitive mechanisms of nicotine on visual attention. Neuron 36, 539-548 (2002).
192. Giessing, C., Thiel, C. M., Rösler, F. & Fink, G. R. The modulatory effects of nicotine on parietal cortex activity in a cued target detection task depend on cue reliability. Neuroscience 137, 853-864 (2006).
193. Christensen, J. K., Moller, I. W., Ronsted, P., Angelo, H. R. & Johansson, B. Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies. Pharmacol. Toxicol. 68, 163-165 (1991).
194. Goedde, H. W., Agarwal, D. P. & Harada, S. in Isozymes: Current Topics in Biological and Medical Research: Cellular Localization, Metabolism, and Physiology Vol. 8 (eds Rattazzi, M. C., Scandalios, J. G. & Whitt, G. S.) 175-193 (Liss, New York, 1983).
195. Volpicelli, J. R., Alterman, A. I., Hayashida, M. & O'Brien, C. P. Naltrexone in the treatment of alcohol dependence. Arch. Gen. Psychiatry 49, 876-880 (1992).
196. O'Malley, S. S. et al. Naltrexone and coping skills therapy for alcohol dependence: A controlled study. Arch. Gen. Psychiatry 49, 881-887 (1992).
197. Hurt, R. D. et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N. Engl. J. Med. 337, 1195-1202 (1997).
198. Mason, B. J. Acamprosate and naltrexone treatment for alcohol dependence: An evidence-based risk-benefits assessment. Eur. Neuropsychopharmacol. 13, 469-475 (2003).
199. Mason, B. J., Goodman, A. M., Chabac, S. & Lehert, P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: The role of patient motivation. J. Psychiatr. Res. 40, 383-393 (2006).
200. Jorenby, D. E. et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. J. Am. Med. Assoc. 296, 56-63 (2006); erratum 296, 1355 (2006).
201. Altshuler, H. L., Phillips, P. E. & Feinhandler, D. A. Alteration of ethanol self-administration by naltrexone. Life Sci. 26, 679-688 (1980).
202. Heyser, C. J., Moc, K. & Koob, G. F. Effects of naltrexone alone and in combination with acamprosate on the alcohol deprivation effect in rats. Neuropsychopharmacology 28, 1463-1471 (2003).
203. Colombo, G. et al. Ability of baclofen in reducing alcohol intake and withdrawal severity: I. Preclinical evidence. Alcohol. Clin. Exp. Res. 24, 58-66 (2000).
204. Backstrom, P. & Hyytia, P. Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3, 4-DCPG. Eur. J. Pharmacol. 528, 110-118 (2005).
205. Le Magnen, J., Tran, G., Durlach, J. & Martin, C. Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate. Alcohol 4, 97-102 (1987).
206. Liu, X. & Weiss, F. Additive effect of stress and drug cues on reinstatement of ethanol seeking: Exacerbation by history of dependence and role of concurrent activation of corticotropin-releasing factor and opioid mechanisms. J. Neurosci. 22, 7856-7861 (2002).
207. Bachteler, D., Economidou, D., Danysz, W., Ciccocioppo, R. & Spanagel, R. The effects of acamprosate and neramexane on cue-induced reinstatement of ethanol-seeking behavior in rat. Neuropsychopharmacology 30, 1104-1110 (2005).
208. Maccioni, P., Bienkowski, P., Carai, M. A., Gessa, G. L. & Colombo, G. Baclofen attenuates cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats. Drug Alcohol Depend. 95, 284-287 (2008).
209. Le, A. D., Harding, S., Juzytsch, W., Funk, D. & Shaham, Y. Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats. Psychopharmacology 179 366-373 (2005).