1932

Abstract

The identification of a heuristic framework for the stages of the addiction cycle that are linked to neurocircuitry changes in pathophysiology includes the binge/intoxication stage, the withdrawal/negative affect stage, and the preoccupation/anticipation (craving) stage, which represent neuroadaptations in three neurocircuits (basal ganglia, extended amygdala, and frontal cortex, respectively). The identification of excellent and validated animal models, the development of human laboratory models, and an enormous surge in our understanding of neurocircuitry and neuropharmacological mechanisms have provided a revisionist view of addiction that emphasizes the loss of brain reward function and gain of stress function that drive negative reinforcement (the dark side of addiction) as a key to compulsive drug seeking. Reversing the dark side of addiction not only explains much of the existing successful pharmacotherapies for addiction but also points to vast new opportunities for future medications to alleviate this major source of human suffering.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-010715-103143
2016-01-06
2024-12-10
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/56/1/annurev-pharmtox-010715-103143.html?itemId=/content/journals/10.1146/annurev-pharmtox-010715-103143&mimeType=html&fmt=ahah

Literature Cited

  1. Koob GF, Le Moal M. 1.  2008. Addiction and the brain antireward system. Annu. Rev. Psychol. 59:29–53 [Google Scholar]
  2. Piazza PV, Deroche V, Deminiere JM, Maccari S, Le Moal M, Simon H. 2.  1993. Corticosterone in the range of stress-induced levels possesses reinforcing properties: implications for sensation-seeking behaviors. PNAS 90:11738–42 [Google Scholar]
  3. Koob GF, Lloyd GK, Mason BJ. 3.  2009. Development of pharmacotherapies for drug addiction: a Rosetta Stone approach. Nat. Rev. Drug Discov. 8:500–15 [Google Scholar]
  4. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J. 4.  et al. 2007. Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J. Neurosci. 27:12700–6 [Google Scholar]
  5. Mitchell JM, O'Neil JP, Janabi M, Marks SM, Jagust WJ, Fields HL. 5.  2012. Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens. Sci. Trans. Med. 4:116ra6 [Google Scholar]
  6. Heimer L, Alheid G. 6.  1991. Piecing together the puzzle of basal forebrain anatomy. The Basal Forebrain: Anatomy to Function TC Napier, PW Kalivas, I Hanin 1–42 New York: Plenum [Google Scholar]
  7. Carlezon WA Jr, Nestler EJ, Neve RL. 7.  2000. Herpes simplex virus-mediated gene transfer as a tool for neuropsychiatric research. Crit. Rev. Neurobiol. 14:47–67 [Google Scholar]
  8. Jonas DE, Amick HR, Feltner C, Bobashev G, Thomas K. 8.  et al. 2014. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 311:1889–900 [Google Scholar]
  9. Dole VP. 9.  1988. Implications of methadone maintenance for theories of narcotic addiction. JAMA 260:3025–29 [Google Scholar]
  10. Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A. 10.  et al. 2004. Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology 29:158–70 [Google Scholar]
  11. Evans DE, Drobes DJ. 11.  2009. Nicotine self-medication of cognitive-attentional processing. Addict. Biol. 14:32–42 [Google Scholar]
  12. Kassel JD, Unrod M. 12.  2000. Smoking, anxiety, and attention: support for the role of nicotine in attentionally mediated anxiolysis. J. Abnorm. Psychol. 109:161–66 [Google Scholar]
  13. Koob GF, Kreek MJ. 13.  2007. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am. J. Psychiatry 164:1149–59 [Google Scholar]
  14. Marlatt G, Gordon J. 14.  1980. Determinants of relapse: implications for the maintenance of behavioral change. Behavioral Medicine: Changing Health Lifestyles P Davidson, S Davidson 410–52 New York: Brunner/Mazel [Google Scholar]
  15. Mason BJ, Light JM, Williams LD, Drobes DJ. 15.  2009. Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin. Addict. Biol. 14:73–83 [Google Scholar]
  16. Mason BJ, Light JM, Escher T, Drobes DJ. 16.  2008. Effect of positive and negative affective stimuli and beverage cues on measures of craving in non treatment-seeking alcoholics. Psychopharmacology 200:141–50 [Google Scholar]
  17. Sinha R. 17.  2009. Modeling stress and drug craving in the laboratory: implications for addiction treatment development. Addict. Biol. 14:84–98 [Google Scholar]
  18. Lang P, Kozak MJ, Miller GA, Levin DN, McLean A Jr. 18.  1980. Emotional imagery: conceptual structure and pattern of somatovisceral response. Psychophysiology 17:179–92 [Google Scholar]
  19. Fox HC, Talih M, Malison R, Anderson GM, Kreek MJ, Sinha R. 19.  2005. Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues. Psychoneuroendicrinology 30:880–91 [Google Scholar]
  20. al'Absi M, Hatsukami D, Davis GL. 20.  2005. Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse. Psychopharmacology 181:107–17 [Google Scholar]
  21. Higley AE, Crane NA, Spadoni AD, Quello SB, Goodell V, Mason BJ. 21.  2011. Craving in response to stress induction in a human laboratory paradigm predicts treatment outcome in alcohol-dependent individuals. Psychopharmacology 218:121–29 [Google Scholar]
  22. Vendruscolo LF, Estey D, Goodell V, Macshane LG, Logrip ML. 22.  et al. 2015. Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. J. Clin. Investig. 125:3193–97 [Google Scholar]
  23. Mason BJ, Goodman AM, Chabac S, Lehert P. 23.  2006. 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. 40:383–93 [Google Scholar]
  24. Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. 24.  2014. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern. Med. 174:70–77 [Google Scholar]
  25. Shaham Y, Shalev U, Lu L, de Wit H, Stewart J. 25.  2003. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20 [Google Scholar]
  26. Schultz W. 26.  2007. Multiple dopamine functions at different time courses. Annu. Rev. Neurosci. 30:259–88 [Google Scholar]
  27. Le Merrer J, Becker JA, Befort K, Kieffer BL. 27.  2009. Reward processing by the opioid system in the brain. Physiol. Rev. 89:1379–412 [Google Scholar]
  28. Tolu S, Eddine R, Marti F, David V, Graupner M. 28.  et al. 2013. Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement. Mol. Psychiatry 18:382–93 [Google Scholar]
  29. Weiss F, Markou A, Lorang MT, Koob GF. 29.  1992. Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res. 593:314–18 [Google Scholar]
  30. Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL. 30.  1993. Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. PNAS 90:7966–69 [Google Scholar]
  31. Diana M, Pistis M, Muntoni A, Gessa G. 31.  1995. Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats. J. Pharmacol. Exp. Ther. 272:781–85 [Google Scholar]
  32. Nestler EJ. 32.  1996. Under siege: the brain on opiates. Neuron 16:897–900 [Google Scholar]
  33. Weiss F, Parsons LH, Schulteis G, Hyytia P, Lorang MT. 33.  et al. 1996. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J. Neurosci. 16:3474–85 [Google Scholar]
  34. Melis M, Spiga S, Diana M. 34.  2005. The dopamine hypothesis of drug addiction: hypodopaminergic state. Int. Rev. Neurobiol. 63:101–54 [Google Scholar]
  35. Collier HO. 35.  1980. Cellular site of opiate dependence. Nature 283:625–29 [Google Scholar]
  36. Koob GF, Volkow ND. 36.  2010. Neurocircuitry of addiction. Neuropsychopharmacol. Rev. 35:217–38 Erratum. 2010 Neuropsychopharmacol. Rev. 35:1051 [Google Scholar]
  37. Mello NK, Mendelson JH. 37.  1980. Buprenorphine suppresses heroin use by heroin addicts. Science 207:657–59 [Google Scholar]
  38. Tzschentke TM. 38.  2002. Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction. Psychopharmacology 161:1–16 [Google Scholar]
  39. Cowan A. 39.  2007. Buprenorphine: the basic pharmacology revisited. J. Addict. Med. 1:68–72 [Google Scholar]
  40. Wade CL, Vendruscolo LF, Schlosburg JE, Hernandez DO, Koob GF. 40.  2015. Compulsive-like responding for opioid analgesics in rats with extended access. Neuropsychopharmacology 40:421–28 [Google Scholar]
  41. Negus SS, Woods JH. 41.  1995. Reinforcing effects, discriminative stimulus effects and physical dependence liability of buprenorphine. Buprenorphine: Combatting Drug Abuse with a Unique Opioid A Cowan, JW Lewis 71–101 New York: Wiley-Liss [Google Scholar]
  42. Mello NK, Lukas SE, Bree MP, Mendelson JH. 42.  1988. Progressive ratio performance maintained by buprenorphine, heroin and methadone in Macaque monkeys. Drug Alcohol Depend. 21:81–97 [Google Scholar]
  43. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. 43.  1976. The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther. 197:517–32 [Google Scholar]
  44. Jasinski DR, Pevnick JS, Griffith JD. 44.  1978. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch. Gen. Psychiatry 35:501–16 [Google Scholar]
  45. Mello NK, Bree MP, Mendelson JH. 45.  1983. Comparison of buprenorphine and methadone effects on opiate self-administration in primates. J. Pharmacol. Exp. Ther. 225:378–86 [Google Scholar]
  46. Winger G, Skjoldager P, Woods JH. 46.  1992. Effects of buprenorphine and other opioid agonists and antagonists on alfentanil- and cocaine-reinforced responding in rhesus monkeys. J. Pharmacol. Exp. Ther. 261:311–17 [Google Scholar]
  47. Comer SD, Collins ED, Fischman MW. 47.  2001. Buprenorphine sublingual tablets: effects on IV heroin self-administration by humans. Psychopharmacology 154:28–37 [Google Scholar]
  48. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ. 48.  et al. 2006. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56–63 Erratum. 2006 JAMA 296:1355 [Google Scholar]
  49. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS. 49.  et al. 2007. Pharmacological profile of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology 52:985–94 [Google Scholar]
  50. Biala G, Staniak N, Budzynska B. 50.  2010. Effects of varenicline and mecamylamine on the acquisition, expression, and reinstatement of nicotine-conditioned place preference by drug priming in rats. Naunyn Schmiedeberg's Arch. Pharmacol. 381:361–70 [Google Scholar]
  51. Spiller K, Xi ZX, Li X, Ashby CR Jr, Callahan PM. 51.  et al. 2009. Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of α4β2 nicotinic receptors in rats. Neuropharmacology 57:60–66 [Google Scholar]
  52. Smith JW, Mogg A, Tafi E, Peacey E, Pullar IA. 52.  et al. 2007. Ligands selective for α4β2 but not α3β4 or α7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat. Psychopharmacology 190:157–70 [Google Scholar]
  53. Igari M, Alexander JC, Ji Y, Qi X, Papke RL, Bruijnzeel AW. 53.  2014. Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats. Neuropsychopharmacology 39:455–65 [Google Scholar]
  54. Foulds J, Russ C, Yu CR, Zou KH, Galaznik A. 54.  et al. 2013. Effect of varenicline on individual nicotine withdrawal symptoms: a combined analysis of eight randomized, placebo-controlled trials. Nicotine Tob. Res. 15:1849–57 [Google Scholar]
  55. George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP. 55.  et al. 2007. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. PNAS 104:17198–203 [Google Scholar]
  56. George O, Lloyd A, Carroll FI, Damaj MI, Koob GF. 56.  2011. Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. Psychopharmacology 213:715–22 [Google Scholar]
  57. Pulvirenti L, Koob GF. 57.  2002. Being partial to psychostimulant addiction therapy. Trends Pharmacol. Sci. 23:151–53 [Google Scholar]
  58. Wee S, Wang Z, Woolverton WL, Pulvirenti L, Koob GF. 58.  2007. Effect of aripiprazole, a partial D2 receptor agonist, on increased rate of methamphetamine self-administration in rats with prolonged access. Neuropsychopharmacology 32:2238–47 [Google Scholar]
  59. Vergne DE, Anton RF. 59.  2010. Aripiprazole: a drug with a novel mechanism of action and possible efficacy for alcohol dependence. CNS Neurol. Disord. Drug Targets 9:50–54 [Google Scholar]
  60. de Witte P, Littleton J, Parot P, Koob G. 60.  2005. Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action. CNS Drugs 19:517–37 [Google Scholar]
  61. Littleton JM. 61.  2007. Acamprosate in alcohol dependence: implications of a unique mechanism of action. J. Addict. Med. 1:115–25 [Google Scholar]
  62. Spanagel R, Kiefer F. 62.  2008. Drugs for relapse prevention of alcoholism: ten years of progress. Trends Pharmacol. Sci. 29:109–15 [Google Scholar]
  63. Kalivas PW, McFarland K, Bowers S, Szumlinski K, Xi ZX, Baker D. 63.  2003. Glutamate transmission and addiction to cocaine. Glutamate and Disorders of Cognition and Motivation B Moghaddam, ME Wolf 169–75 New York: N.Y. Acad. Sci. [Google Scholar]
  64. Everitt BJ, Wolf ME. 64.  2002. Psychomotor stimulant addiction: a neural systems perspective. J. Neurosci. 22:3312–20 Erratum. 2002 J. Neurosci. 22:161a [Google Scholar]
  65. Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL. 65.  2001. Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292:1175–78 [Google Scholar]
  66. Backstrom P, Hyytia P. 66.  2006. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology 31:778–86 [Google Scholar]
  67. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. 67.  2000. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 41:Suppl. 1S3–9 [Google Scholar]
  68. Stringer S, Rueve M, Mossman D. 68.  2008. Topiramate as treatment for alcohol dependence. J. Am. Med. Assoc. 299:405–6 [Google Scholar]
  69. Olmsted CL, Kockler DR. 69.  2008. Topiramate for alcohol dependence. Ann. Pharmacother. 42:1475–80 [Google Scholar]
  70. Farook JM, Lewis B, Littleton JM, Barron S. 70.  2009. Topiramate attenuates the stress-induced increase in alcohol consumption and preference in male C57BL/6J mice. Physiol. Behav. 96:189–93 [Google Scholar]
  71. Koob GF. 71.  2008. A role for brain stress systems in addiction. Neuron 59:11–34 [Google Scholar]
  72. Koob GF. 72.  2013. Addiction is a reward deficit and stress surfeit disorder. Front. Psychiatry 4:72 [Google Scholar]
  73. Vendruscolo LF, Barbier E, Schlosburg JE, Misra KK, Whitfield T Jr. 73.  et al. 2012. Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. J. Neurosci. 32:7563–71 [Google Scholar]
  74. Bruijnzeel AW, Zislis G, Wilson C, Gold MS. 74.  2007. Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 32:955–63 [Google Scholar]
  75. Bruijnzeel AW, Small E, Pasek TM, Yamada H. 75.  2010. Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats. Behav. Brain Res. 210:288–91 [Google Scholar]
  76. Specio SE, Wee S, O'Dell LE, Boutrel B, Zorrilla EP, Koob GF. 76.  2008. CRF1 receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology 196:473–82 [Google Scholar]
  77. Greenwell TN, Funk CK, Cottone P, Richardson HN, Chen SA. 77.  et al. 2009. Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats. Addict. Biol. 14:130–43 [Google Scholar]
  78. Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF. 78.  2007. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol. Psychiatry 61:78–86 [Google Scholar]
  79. Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR. 79.  et al. 2008. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala Crhr1 expression following a history of dependence. Biol. Psychiatry 63:139–45 [Google Scholar]
  80. Valdez GR, Roberts AJ, Chan K, Davis H, Brennan M. 80.  et al. 2002. Increased ethanol self-administration and anxiety-like behavior during acute withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol. Clin. Exp. Res. 26:1494–501 [Google Scholar]
  81. Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hipskind PA. 81.  et al. 2007. 3-(4-Chloro-2-morpholin-4-yl-thiazol-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. 27:2718–26 [Google Scholar]
  82. Funk CK, O'Dell LE, Crawford EF, Koob GF. 82.  2006. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J. Neurosci. 26:11324–32 [Google Scholar]
  83. Nestler EJ. 83.  2004. Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol. Sci. 25:210–18 [Google Scholar]
  84. Shippenberg TS, Zapata A, Chefer VI. 84.  2007. Dynorphin and the pathophysiology of drug addiction. Pharmacol. Ther. 116:306–21 [Google Scholar]
  85. Wee S, Koob GF. 85.  2010. The role of the dynorphin-κ opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology 210:121–35 [Google Scholar]
  86. Wee S, Orio L, Ghirmai S, Cashman JR, Koob GF. 86.  2009. Inhibition of κ opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine. Psychopharmacology 205:565–75 [Google Scholar]
  87. Walker BM, Zorrilla EP, Koob GF. 87.  2010. Systemic κ-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats. Addict. Biol. 16:116–19 [Google Scholar]
  88. Schlosburg JE, Whitfield TW Jr, Park PE, Crawford EF, George O. 88.  et al. 2013. Long-term antagonism of κ opioid receptors prevents escalation of and increased motivation for heroin intake. J. Neurosci. 33:19384–92 [Google Scholar]
  89. Whitfield TW Jr, Schlosburg J, Wee S, Vendruscolo L, Gould A. 89.  et al. 2015. κ opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake. J. Neurosci. 35:104296–305 [Google Scholar]
  90. Nealey KA, Smith AW, Davis SM, Smith DG, Walker BM. 90.  2011. κ-Opioid receptors are implicated in the increased potency of intra-accumbens nalmefene in ethanol-dependent rats. Neuropharmacology 61:35–42 [Google Scholar]
  91. Barbier E, Vendruscolo LF, Schlosburg JE, Edwards S, Juergens N. 91.  et al. 2013. The NK1 receptor antagonist L822429 reduces heroin reinforcement. Neuropsychopharmacology 38:976–84 [Google Scholar]
  92. Schmeichel BE, Barbier E, Misra KK, Contet C, Schlosburg JE. 92.  et al. 2015. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats. Neuropsychopharmacology 40:1123–29 [Google Scholar]
  93. Heilig M, Koob GF. 93.  2007. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 30:399–406 [Google Scholar]
  94. Valdez GR, Koob GF. 94.  2004. Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y systems: implications for the development of alcoholism. Pharmacol. Biochem. Behav. 79:671–89 [Google Scholar]
  95. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C. 95.  et al. 1995. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–35 [Google Scholar]
  96. Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA. 96.  et al. 1995. Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 270:792–94 [Google Scholar]
  97. Ciccocioppo R, Economidou D, Fedeli A, Massi M. 97.  2003. The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats. Physiol. Behav. 79:121–28 [Google Scholar]
  98. Martin-Fardon R, Zorrilla EP, Ciccocioppo R, Weiss F. 98.  2010. Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin. Brain Res. 1314:145–61 [Google Scholar]
  99. Patel S, Roelke CT, Rademacher DJ, Hillard CJ. 99.  2005. Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur. J. Neurosci. 21:1057–69 [Google Scholar]
  100. Serrano A, Parsons LH. 100.  2011. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol. Ther. 132:215–41 [Google Scholar]
  101. Bajo M, Cruz MT, Siggins GR, Messing R, Roberto M. 101.  2008. Protein kinase C ε mediation of CRF- and ethanol-induced GABA release in central amygdala. PNAS 105:8410–15 [Google Scholar]
  102. Roberto M, Gilpin NW, O'Dell LE, Cruz MT, Morse AC. 102.  et al. 2008. Cellular and behavioral interactions of gabapentin with alcohol dependence. J. Neurosci. 28:5762–71 [Google Scholar]
  103. Roberto M, Cruz MT, Gilpin NW, Sabino V, Schweitzer P. 103.  et al. 2010. Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol. Psychiatry 67:831–39 [Google Scholar]
  104. Kallupi M, Wee S, Edwards S, Whitfield TW Jr, Oleata CS. 104.  et al. 2013. κ opioid receptor-mediated dysregulation of GABAergic transmission in the central amygdala in cocaine addiction. Biol. Psychiatry 74:520–28 [Google Scholar]
  105. Roberto M, Gilpin NW. 105.  2014. Central amygdala neuroplasticity in alcohol dependence. Neurobiology of Alcohol Dependence A Noronha, C Cui, A Harris, J Crabbe 207–20 New York: Elsevier [Google Scholar]
  106. Chung K, Deisseroth K. 106.  2013. CLARITY for mapping the nervous system. Nat. Methods 10:508–13 Erratum. 2013 Nat. Methods 10:1035 [Google Scholar]
  107. Nussinov R, Tsai CJ. 107.  2015. The design of covalent allosteric drugs. Annu. Rev. Pharmacol. Toxicol. 55:249–67 [Google Scholar]
  108. Day JJ, Kennedy AJ, Sweatt JD. 108.  2015. DNA methylation and its implications and accessibility for neuropsychiatric therapeutics. Annu. Rev. Pharmacol. Toxicol. 55:591–611 [Google Scholar]
  109. Moonat S, Sakharkar AJ, Zhang H, Pandey SC. 109.  2011. The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism. Addict. Biol. 16:238–50 [Google Scholar]
  110. Treutlein J, Kissling C, Frank J, Wiemann S, Dong L. 110.  et al. 2006. 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 [Google Scholar]
  111. Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M. 111.  2008. Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol. Psychiatry 63:146–51 [Google Scholar]
  112. Schmid B, Blomeyer D, Treutlein J, Zimmermann US, Buchmann AF. 112.  et al. 2010. Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds. Int. J. Neuropsychopharmacol. 13:703–14 [Google Scholar]
  113. Chen AC, Manz N, Tang Y, Rangaswamy M, Almasy L. 113.  et al. 2010. Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. Alcohol. Clin. Exp. Res. 34:988–96 [Google Scholar]
  114. Sommer WH, Lidström J, Sun H, Passer D, Eskay R. 114.  et al. 2010. Human NPY promoter variation rs16147:T>C as a moderator of prefrontal NPY gene expression and negative affect. Hum. Mutat. 31:E1594–608 [Google Scholar]
  115. Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D. 115.  et al. 2008. Genetic variation in human NPY expression affects stress response and emotion. Nature 452:997–1001 [Google Scholar]
  116. Donner J, Sipilä T, Ripatti S, Kananen L, Chen X. 116.  et al. 2012. Support for involvement of glutamate decarboxylase 1 and neuropeptide Y in anxiety susceptibility. Am. J. Med. Genet. B Neuropsychiatr. Genet. 159B:316–27 [Google Scholar]
  117. Wetherill L, Schuckit MA, Hesselbrock V, Xuei X, Liang T. 117.  et al. 2008. Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence. Alcohol. Clin. Exp. Res. 32:2031–40 [Google Scholar]
  118. Bhaskar LV, Thangaraj K, Kumar KP, Pardhasaradhi G, Singh L, Rao VR. 118.  2013. Association between neuropeptide Y gene polymorphisms and alcohol dependence: a case-control study in two independent populations. Eur. Addict. Res. 19:307–13 [Google Scholar]
  119. Mutschler J, Abbruzzese E, von der Goltz C, Dinter C, Mobascher A. 119.  et al. 2012. Genetic variation in the neuropeptide Y gene promoter is associated with increased risk of tobacco smoking. Eur. Addict. Res. 18:246–52 [Google Scholar]
  120. Okahisa Y, Ujike H, Kotaka T, Morita Y, Kodama M. 120.  et al. 2009. Association between neuropeptide Y gene and its receptor Y1 gene and methamphetamine dependence. Psychiatry Clin. Neurosci. 63:417–22 [Google Scholar]
  121. Collins FS, Varmus H. 121.  2015. A new initiative on precision medicine. N. Engl. J. Med. 372:793–95 [Google Scholar]
  122. Insel PA, Amara SG, Blaschke TF. 122.  2015. Introduction to the theme “Precision Medicine and Prediction in Pharmacology.”. Annu. Rev. Pharmacol. Toxicol. 55:11–14 [Google Scholar]
  123. Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U. 123.  et al. 2015. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu. Rev. Pharmacol. Toxicol. 55:89–106 [Google Scholar]
  124. Gross ER, Zambelli VO, Small BA, Ferreira JC, Chen CH, Mochly-Rosen D. 124.  2015. A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annu. Rev. Pharmacol. Toxicol. 55:107–27 [Google Scholar]
  125. Chu K, Koob GF, Cole M, Zorrilla EP, Roberts AJ. 125.  2007. 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. 86:813–21 [Google Scholar]
  126. Gilpin NW, Misra K, Koob GF. 126.  2008. Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced increases in alcohol drinking. Pharmacol. Biochem. Behav. 90:475–80 [Google Scholar]
  127. Overstreet DH, Knapp DJ, Breese GR. 127.  2007. Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol. Clin. Exp. Res. 31:1473–81 [Google Scholar]
  128. Sabino V, Cottone P, Koob GF, Steardo L, Lee MJ. 128.  et al. 2006. Dissociation between opioid and CRF1 antagonist sensitive drinking in Sardinian alcohol-preferring rats. Psychopharmacology 189:175–86 [Google Scholar]
  129. Richardson HN, Zhao Y, Fekete EM, Funk CK, Wirsching P. 129.  et al. 2008. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist. Pharmacol. Biochem. Behav. 88:497–510 [Google Scholar]
  130. Walker BM, Rasmussen DD, Raskind MA, Koob GF. 130.  2008. α1-Noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol 42:91–97 [Google Scholar]
  131. Skelly MJ, Weiner JL. 131.  2014. Chronic treatment with prazosin or duloxetine lessens concurrent anxiety-like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety-related alcohol use. Brain Behav. 4:468–83 [Google Scholar]
  132. Gilpin NW, Koob GF. 132.  2010. Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats. Psychopharmacology 212:431–39 [Google Scholar]
  133. Walker BM, Koob GF. 133.  2008. Pharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence. Neuropsychopharmacology 33:643–52 [Google Scholar]
  134. Walker BM, Koob GF. 134.  2007. The γ-aminobutyric acid-B receptor agonist baclofen attenuates responding for ethanol in ethanol-dependent rats. Alcohol. Clin. Exp. Res. 31:11–18 [Google Scholar]
  135. Gilpin NW. 135.  2012. Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence. Neuropeptides 46:253–59 [Google Scholar]
  136. Rimondini R, Thorsell A, Heilig M. 136.  2005. Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y2 receptor antagonist BIIE0246: evidence for sensitization in rats with a history of dependence. Neurosci. Lett. 375:129–33 [Google Scholar]
  137. Gilpin NW, Richardson HN, Koob GF. 137.  2008. Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats. Alcohol. Clin. Exp. Res. 32:1535–42 [Google Scholar]
  138. Abulseoud OA, Camsari UM, Ruby CL, Kasasbeh A, Choi S, Choi DS. 138.  2014. Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2. Neuropsychopharmacology 39:1674–84 [Google Scholar]
  139. Hinton DJ, Lee MR, Jacobson TL, Mishra PK, Frye MA. 139.  et al. 2012. Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1. Neuropharmacology 62:2480–88 [Google Scholar]
  140. Griffin WC III, Haun HL, Hazelbaker CL, Ramachandra VS, Becker HC. 140.  2014. Increased extracellular glutamate in the nucleus accumbens promotes excessive ethanol drinking in ethanol dependent mice. Neuropsychopharmacology 39:707–17 [Google Scholar]
  141. Alaux-Cantin S, Buttolo R, Houchi H, Jeanblanc J, Naassila M. 141.  2015. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats. Addict. Biol. 20:890–901 [Google Scholar]
  142. Smith AW, Nealey KA, Wright JW, Walker BM. 142.  2011. Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems. Neurobiol. Learn. Mem. 96:199–206 [Google Scholar]
  143. Qiang M, Li JG, Denny AD, Yao JM, Lieu M. 143.  et al. 2014. Epigenetic mechanisms are involved in the regulation of ethanol consumption in mice. Int. J. Neuropsychopharmacol. 18:21–11 [Google Scholar]
  144. Koob GF. 144.  2015. The dark side of emotion: the addiction perspective. Eur. J. Pharmacol. 753:73–87 [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-010715-103143
Loading
/content/journals/10.1146/annurev-pharmtox-010715-103143
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error