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Allostasis and Addiction

An overall conceptual framework throughout this review is that drug dependence represents a break with homeostatic brain regulatory mechanisms that regulate the emotional state of the animal. However, the nature of engagement of the brain stress and antistress systems produced by repeated self-administration of drugs of abuse argues that the view of drug addiction representing a simple break with homeostasis is not sufficient to explain a number of key elements of addiction. Drug addiction, similar to other chronic physiological disorders, such as high blood pressure, worsens over time, is subject to significant environmental influences (e.g., external stressors), and leaves a residual neural trace that allows rapid ?readdiction? even months and years after detoxification and abstinence. These characteristics of drug addiction have led to a reconsideration of drug addiction as more than simply homeostatic dysregulation of emotional function but rather as a dynamic break with homeostasis of these systems, termed allostasis.

Allostasis is defined as ?stability through change? and is different from homeostasis because feed-forward, rather than negative feedback, mechanisms are hypothesized to be engaged (Sterling and Eyer, 1988). However, precisely this ability to mobilize resources quickly and to use feed-forward mechanisms leads to an allostatic state if the systems do not have sufficient time to reestablish homeostasis. An allostatic state can be defined as a state of chronic deviation of the regulatory system from its normal (homeostatic) operating level.

The brain stress systems respond rapidly to anticipated challenges to homeostasis but are slow to habituate or do not readily shut off once engaged (Koob, 1999). Thus, the very physiological mechanism that allows a rapid and sustained response to environmental challenge becomes the engine of pathology if adequate time or resources are not available to shut off the response. Thus, the interaction between CRF and norepinephrine in the brainstem and basal forebrain, the interaction between orexin and CRF in the hypothalamus and basal forebrain, and the interaction between CRF and vasopressin and/or orexin could lead to chronically dysregulated emotional states (Koob, 1999). Similar allostatic mechanisms can be hypothesized to be involved in driving the pathology associated with the brain stress and antistress systems in addiction (Koob and Le Moal, 2001). Repeated challenges (e.g., with drugs of abuse) lead to attempts of the brain via molecular, cellular, and neurocircuitry changes to maintain stability, but at a cost. For the drug addiction framework elaborated here, the residual deviation from normal brain reward threshold regulation is termed an allostatic state. This state represents a combination of chronic elevation of reward set point fueled by numerous neurobiological changes, including decreased function of reward circuits, loss of executive control, and facilitation of stimulus-response associations, but also recruitment of the brain stress systems and compromises to the brain antistress systems. All of these effects contribute to the compulsivity of drug seeking and drug taking known as addiction (Koob and Le Moal, 2008).

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This work was supported by National Institutes of Health funding from the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute of Diabetes and Digestive and Kidney Diseases, and private funding from the Pearson Center for Alcoholism and Addiction Research. The author would like to thank Michael Arends and Mellany Santos for their help with manuscript preparation, Janet Hightower for her invaluable assistance with the figures, Dr. Charles Neal for his work on the neuroanatomical distribution of nociceptin (Neal et al., 1999) and for his help with Figure 9, and Dr. Michel Le Moal for discussions and the conceptual framework. The author also would like to thank the following people for critical comments and discussions on the manuscript: Dr. Heather Richardson, Dr. Scott Edwards, Dr. Dong Ji, Dr. Kaushik Misra, Dr. Laura Orio, Dr. Nick Gilpin, Dr. Olivier George, Dr. Marisa Roberto, Dr. Sunmee Wee, and Dr. Benjamin Boutrel. This is publication number 19397 from The Scripps Research Institute.

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The Supplemental Data can be found with this article online at http://www.neuron.org/cgi/content/full/59/1/11/DC1/.

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  1. Adrian TE, Allen JM, Bloom SR, Ghatei MA, Rossor MN, Roberts GW, Crow TJ, Tatemoto K, Polak JM. Neuropeptide Y distribution in human brain. Nature. 1983;306:584?586. [PubMed]
  2. Ahmed SH, Koob GF. Transition from moderate to excessive drug intake: change in hedonic set point. Science. 1998;282:298?300. [PubMed]
  3. Ahmed SH, Walker JR, Koob GF. Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology. 2000;22:413?421. [PubMed]
  4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4. Washington, DC: American Psychiatric Press; 1994.
  5. Anton B, Fein J, To T, Li X, Silberstein L, Evans CJ. Immunohistochemical localization of ORL-1 in the central nervous system of the rat. J Comp Neurol. 1996;368:229?251. [PubMed]
  6. Aston-Jones G, Delfs JM, Druhan J, Zhu Y. The bed nucleus of the stria terminalis: A target site for noradrenergic actions in opiate withdrawal. In: McGinty JF, editor. Advancing from the Ventral Striatum to the Extended Amygdala: Implications for Neuropsychiatry and Drug Abuse (series title: Annals of the New York Academy of Sciences, vol. 877) New York: New York Academy of Sciences; 1999. pp. 486?498. [PubMed]
  7. Badia-Elder NE, Stewart RB, Powrozek TA, Roy KF, Murphy JM, Li TK. Effect of neuropeptide Y (NPY) on oral ethanol intake in Wistar, alcohol-preferring (P), and -nonpreferring (NP) rats. Alcohol Clin Exp Res. 2001;25:386?390. [PubMed]
  8. Badia-Elder NE, Stewart RB, Powrozek TA, Murphy JM, Li TK. Effects of neuropeptide Y on sucrose and ethanol intake and on anxiety-like behavior in high alcohol drinking (HAD) and low alcohol drinking (LAD) rats. Alcohol Clin Exp Res. 2003;27:894?899. [PubMed]
  9. Baldo BA, Daniel RA, Berridge CW, Kelley AE. Overlapping distributions of orexin/hypocretin- and dopamine-β-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol. 2003;464:220?237. [PubMed]
  10. Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT. CRF antagonist reverses the ?anxiogenic? response to ethanol withdrawal in the rat. Psychopharmacology (Berl) 1991;103:227?232. [PubMed]
  11. Bale TL, Vale WW. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol. 2004;44:525?557. [PubMed]
  12. Basso AM, Spina M, Rivier J, Vale W, Koob GF. 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 (Berl) 1999;145:21?30. [PubMed]
  13. Beardsley PM, Howard JL, Shelton KL, Carroll FI. 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 (Berl) 2005;183:118?126. [PubMed]
  14. Bernard JF, Besson JM. The spino(trigemino)pontoamygdaloid pathway: electrophysiological evidence for an involvement in pain processes. J Neurophysiol. 1990;63:473?490. [PubMed]
  15. Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M. Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry. 2008;63:146?151. [PubMed]
  16. Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF, de Lecea L. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci USA. 2005;102:19168?19173. [PMC free article] [PubMed]
  17. Breese GR, Overstreet DH, Knapp DJ, Navarro M. Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior: inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1a-receptor agonist. Neuropsychopharmacology. 2005;30:1662?1669. [PMC free article] [PubMed]
  18. Bruijnzeel AW, Gold MS. The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev. 2005;49:505?528. [PubMed]
  19. Bruijnzeel AW, Marcinkiewcz C, Isaac S, Booth MM, Dennis DM, Gold MS. The effects of buprenorphine on fentanyl withdrawal in rats. Psychopharmacology (Berl) 2007;191:931?941. [PubMed]
  20. Burchfield S. The stress response: a new perspective. Psychosom Med. 1979;41:661?672. [PubMed]
  21. Caille S, Espejo EF, Reneric JP, Cador M, Koob GF, Stinus L. Total neurochemical lesion of noradrenergic neurons of the locus coeruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal. J Pharmacol Exp Ther. 1999;290:881?892. [PubMed]
  22. Cappendijk SL, Hurd YL, Nylander I, van Ree JM, Terenius L. A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides. Eur J Pharmacol. 1999;365:175?182. [PubMed]
  23. Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G. Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci. 2001;21:4074?4080. [PubMed]
  24. Chavkin C, James IF, Goldstein A. Dynorphin is a specific endogenous ligand of the κ opioid receptor. Science. 1982;215:413?415. [PubMed]
  25. Ciccocioppo R, Panocka I, Polidori C, Regoli D, Massi M. Effect of nociceptin on alcohol intake in alcohol-preferring rats. Psychopharmacology (Berl) 1999;141:220?224. [PubMed]
  26. Ciccocioppo R, Economidou D, Fedeli A, Massi M. 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. 2003;79:121?128. [PubMed]
  27. Ciccocioppo R, Economidou D, Fedeli A, Angeletti S, Weiss F, Heilig M, Massi M. Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats. Psychopharmacology (Berl) 2004;172:170?178. [PMC free article] [PubMed]
  28. Clausen TR, Moller M, Woldbye DP. Inhibitory effect of neuropeptide Y on morphine withdrawal is accompanied by reduced c-fos expression in specific brain regions. J Neurosci Res. 2001;64:410?417. [PubMed]
  29. Contarino A, Papaleo F. The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. Proc Natl Acad Sci USA. 2005;102:18649?18654. [PMC free article] [PubMed]
  30. Darland T, Heinricher MM, Grandy DK. Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more. Trends Neurosci. 1998;21:215?221. [PubMed]
  31. Daunais JB, Roberts DC, McGinty JF. Cocaine self-administration increases preprodynorphin, but not c-fos, mRNA in rat striatum. Neuroreport. 1993;4:543?546. [PubMed]
  32. Davis M, Rainnie D, Cassell M. Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci. 1994;17:208?214. [PubMed]
  33. Day HE, Curran EJ, Watson SJ, Jr, Akil H. Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1β J Comp Neurol. 1999;413:113?128. [PubMed]
  34. de Vries GJ, Miller MA. Anatomy and function of extrahypothalamic vasopressin systems in the brain. In: Urban IJA, Burbach JPH, de Wied D, editors. Advances in Brain Vasopressin (series title: Progress in Brain Research, vol 119) New York: Elsevier; 1998. pp. 3?20. [PubMed]
  35. Delfs JM, Zhu Y, Druhan JP, Aston-Jones G. Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature. 2000;403:430?434. [PubMed]
  36. D?Este L, Casini A, Pontieri FE, Renda TG. Changes in neuropeptide FF and NPY immunohistochemical patterns in rat brain under heroin treatment. Brain Res. 2006;1083:151?158. [PubMed]
  37. Dumont EC, Williams JT. Noradrenaline triggers GABAA inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area. J Neurosci. 2004;24:8198?8204. [PubMed]
  38. Economidou D, Fedeli A, Martin-Fardon R, Weiss F, Massi M, Ciccocioppo R. Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats. Peptides. 2006;27:3299?3306. [PMC free article] [PubMed]
  39. Edwards S, Graham DL, Bachtell RK, Self DW. Region-specific tolerance to cocaine-regulated cAMP-dependent protein phosphorylation following chronic self-administration. Eur J Neurosci. 2007;25:2201?2213. [PubMed]
  40. Egli RE, Kash TL, Choo K, Savchenko V, Matthews RT, Blakely RD, Winder DG. Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis. Neuropsychopharmacology. 2005;30:657?668. [PubMed]
  41. Erb S, Stewart J. A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci. 1999;19:RC35. [PubMed]
  42. Erb S, Shaham Y, Stewart J. The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats. J Neurosci. 1998;18:5529?5536. [PubMed]
  43. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J. α2 Adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology. 2000;23:138?150. [PubMed]
  44. Erb S, Salmaso N, Rodaros D, Stewart J. A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 2001;158:360?365. [PubMed]
  45. Fahlke C, Hård E, Hansen S. Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone. Psychopharmacology (Berl) 1996;127:133?139. [PubMed]
  46. Fallon JH, Leslie FM. Distribution of dynorphin and enkephalin peptides in the rat brain. J Comp Neurol. 1986;249:293?336. [PubMed]
  47. Forray MI, Bustos G, Gysling K. Noradrenaline inhibits glutamate release in the rat bed nucleus of the stria terminalis: in vivo microdialysis studies. J Neurosci Res. 1999;55:311?320. [PubMed]
  48. Fu Y, Matta SG, Brower VG, Sharp BM. Norepinephrine secretion in the hypothalamic paraventricular nucleus of rats during unlimited access to self-administered nicotine: an in vivo microdialysis study. J Neurosci. 2001;21:8979?8989. [PubMed]
  49. Fu Y, Matta SG, Kane VB, Sharp BM. Norepinephrine release in amygdala of rats during chronic nicotine self-administration: an in vivo microdialysis study. Neuropharmacology. 2003;45:514?523. [PubMed]
  50. Fuentealba JA, Forray MI, Gysling K. Chronic morphine treatment and withdrawal increase extracellular levels of norepinephrine in the rat bed nucleus of the stria terminalis. J Neurochem. 2000;75:741?748. [PubMed]
  51. Funk CK, Koob GF. A CRF2 agonist administered into the central nucleus of the amygdala decreases ethanol self-administration in ethanol-dependent rats. Brain Res. 2007;1155:172?178. [PMC free article] [PubMed]
  52. 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. [PubMed]
  53. 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]
  54. Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, et al. 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. 2007;27:2718?2726. [PubMed]
  55. 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?17203. [PMC free article] [PubMed]
  56. Gilpin NW, Stewart RB, Murphy JM, Li TK, Badia-Elder NE. Neuropeptide Y reduces oral ethanol intake in alcohol-preferring (P) rats following a period of imposed ethanol abstinence. Alcohol Clin Exp Res. 2003;27:787?794. [PubMed]
  57. Gilpin NW, Misra K, Koob GF. Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced decreases in alcohol drinking. Pharmacol Biochem Behav. 2008;90:475?480. [PMC free article] [PubMed]
  58. Goeders NE. A neuroendocrine role in cocaine reinforcement. Psychoneuroendocrinology. 1997;22:237?259. [PubMed]
  59. Goeders NE. Stress and cocaine addiction. J Pharmacol Exp Ther. 2002;301:785?789. [PubMed]
  60. Gold MS, Pottash AL, Sweeney DR, Davies RK, Kleber HD. Clonidine decreases opiate withdrawal-related anxiety: possible opiate noradrenergic interaction in anxiety and panic. Subst Alcohol Actions Misuse. 1980;1:239?246. [PubMed]
  61. Greenwood-Van Meerveld B, Gibson M, Gunter W, Shepard J, Foreman R, Myers D. Stereotaxic delivery of corticosterone to the amygdala modulates colonic sensitivity in rats. Brain Res. 2001;893:135?142. [PubMed]
  62. Greenwell TN, Walker BM, Cottone P, Zorrilla EP, Koob GF. The α1 adrenergic receptor antagonist prazosin reduces heroin self-administration in rats with extended access to heroin administration. Pharmacol Biochem Behav. 2008 in press. [PMC free article] [PubMed]
  63. Gulya K, Dave JR, Hoffman PL. Chronic ethanol ingestion decreases vasopressin mRNA in hypothalamic and extrahypothalamic nuclei of mouse brain. Brain Res. 1991;557:129?135. [PubMed]
  64. Hansson AC, Cippitelli A, Sommer WH, Fedeli A, Bjork K, Soverchia L, Terasmaa A, Massi M, Heilig M, Ciccocioppo R. Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc Natl Acad Sci USA. 2006;103:15236?15241. [PMC free article] [PubMed]
  65. Harris GC, Aston-Jones G. Beta-adrenergic antagonists attenuate withdrawal anxiety in cocaine- and morphine-dependent rats. Psychopharmacology (Berl) 1993;113:131?136. [PubMed]
  66. Harris GC, Aston-Jones G. Arousal and reward: a dichotomy in orexin function. Trends Neurosci. 2006;29:571?577. [PubMed]
  67. Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature. 2005;437:556?559. [PubMed]
  68. Hebb DO. Organization of Behavior: A Neuropsychological Theory. New York: Wiley; 1949.
  69. Heilig M. The NPY system in stress, anxiety and depression. Neuropeptides. 2004;38:213?224. [PubMed]
  70. Heilig M, Thorsell A. Brain neuropeptide Y (NPY) in stress and alcohol dependence. Rev Neurosci. 2002;13:85?94. [PubMed]
  71. Heilig M, Koob GF, Ekman R, Britton KT. Corticotropin-releasing factor and neuropeptide Y: role in emotional integration. Trends Neurosci. 1994;17:80?85. [PubMed]
  72. Heimer L, Alheid G. Piecing together the puzzle of basal forebrain anatomy. In: Napier TC, Kalivas PW, Hanin I, editors. The Basal Forebrain: Anatomy to Function (series title: Advances in Experimental Medicine and Biology, vol 295) New York: Plenum Press; 1991. pp. 1?42. [PubMed]
  73. Heinrichs SC, Menzaghi F, Schulteis G, Koob GF, Stinus L. Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav Pharmacol. 1995;6:74?80. [PubMed]
  74. Hennessy JW, Levine S. Stress, arousal, and the pituitary-adrenal system: a psychoendocrine hypothesis. In: Sprague JM, Epstein AN, editors. Progress in Psychobiology and Physiological Psychology. 8. New York: Academic Press; 1979. pp. 133?178.
  75. Himmelsbach CK. Studies on the relation of drug addiction to the autonomic nervous system: results of cold pressor tests. J Pharmacol Exp Ther. 1941;73:91?98.
  76. Holter SM, Henniger MS, Lipkowski AW, Spanagel R. Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats. Psychopharmacology (Berl) 2000;153:93?102. [PubMed]
  77. Huber D, Veinante P, Stoop R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science. 2005;308:245?248. [PubMed]
  78. Imaki T, Nahan JL, Rivier C, Sawchenko PE, Vale W. Differential regulation of corticotropin-releasing factor mRNA in rat brain regions by glucocorticoids and stress. J Neurosci. 1991;11:585?599. [PubMed]
  79. Isoardi NA, Bertotto ME, Martijena ID, Molina VA, Carrer HF. Lack of feedback inhibition on rat basolateral amygdala following stress or withdrawal from sedative-hypnotic drugs. Eur J Neurosci. 2007;26:1036?1044. [PubMed]
  80. Kash TL, Winder DG. Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis. Neuropharmacology. 2006;51:1013?1022. [PubMed]
  81. Khachaturian H, Lewis ME, Schafer MKH, Watson SJ. Anatomy of the CNS opioid systems. Trends Neurosci. 1985;8:111?119.
  82. Kitamura O, Wee S, Specio SE, Koob GF, Pulvirenti L. Escalation of methamphetamine self-administration in rats: a dose-effect function. Psychopharmacology (Berl) 2006;186:48?53. [PubMed]
  83. Knapp DJ, Overstreet DH, Moy SS, Breese GR. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats. Alcohol. 2004;32:101?111. [PMC free article] [PubMed]
  84. Koob GF. Corticotropin-releasing factor, norepinephrine and stress. Biol Psychiatry. 1999;46:1167?1180. [PubMed]
  85. Koob GF. Allostatic view of motivation: implications for psychopathology. In: Bevins RA, Bardo MT, editors. Motivational Factors in the Etiology of Drug Abuse (series title: Nebraska Symposium on Motivation, vol 50) Lincoln NE: University of Nebraska Press; 2004. pp. 1?18.
  86. Koob GF, Bloom FE. Cellular and molecular mechanisms of drug dependence. Science. 1988;242:715?723. [PubMed]
  87. Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997;278:52?58. [PubMed]
  88. Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001;24:97?129. [PubMed]
  89. Koob GF, Le Moal M. Plasticity of reward neurocircuitry and the ?dark side? of drug addiction. Nat Neurosci. 2005;8:1442?1444. [PubMed]
  90. Koob GF, Le Moal M. Neurobiology of Addiction. London: Academic Press; 2006.
  91. Koob GF, Kreek MJ. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry. 2007;164:1149?1159. [PMC free article] [PubMed]
  92. Koob GF, Le Moal M. Addiction and the brain antireward system. Annu Rev Psychol. 2008;59:29?53. [PubMed]
  93. Kovacs KM, Szakall I, O?Brien D, Wang R, Vinod KY, Saito M, Simonin F, Kieffer BL, Vadasz C. Decreased oral self-administration of alcohol in κ-opioid receptor knock-out mice. Alcohol Clin Exp Res. 2005;29:730?738. [PubMed]
  94. Kreek MJ, Koob GF. Drug dependence: Stress and dysregulation of brain reward pathways. Drug Alcohol Depend. 1998;51:23?47. [PubMed]
  95. Kuzmin A, Sandin J, Terenius L, Ogren SO. Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharmacol Exp Ther. 2003;304:310?318. [PubMed]
  96. Kuzmin A, Kreek MJ, Bakalkin G, Liljequist S. The nociceptin/orphanin FQ receptor agonist Ro 64?6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking. Neuropsychopharmacology. 2007;32:902?910. [PubMed]
  97. Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C. The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci. 2008;28:407?414. [PMC free article] [PubMed]
  98. Le AD, Harding S, Juzytsch W, Watchus J, Shalev U, Shaham Y. The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats. Psychopharmacology (Berl) 2000;150:317?324. [PubMed]
  99. Le AD, Harding S, Juzytsch W, Fletcher PJ, Shaham Y. The role of corticotropin-releasing factor in the median raphe nucleus in relapse to alcohol. J Neurosci. 2002;22:7844?7849. [PubMed]
  100. Le AD, 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 (Berl) 2005;179:366?373. [PubMed]
  101. Lee B, Tiefenbacher S, Platt DM, Spealman RD. Pharmacological blockade of α2-adrenoceptors induces reinstatement of cocaine-seeking behavior in squirrel monkeys. Neuropsychopharmacology. 2004;29:686?693. [PubMed]
  102. Leri F, Flores J, Rodaros D, Stewart J. Blockade of stress-induced but not cocaine-induced reinstatement by infusion of noradrenergic antagonists into the bed nucleus of the stria terminalis or the central nucleus of the amygdala. J Neurosci. 2002;22:5713?5718. [PubMed]
  103. Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA. 2001;98:7570?7575. [PMC free article] [PubMed]
  104. Lindholm S, Ploj K, Franck J, Nylander I. Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain. Alcohol. 2000;22:165?171. [PubMed]
  105. 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. 2002;22:7856?7861. [PubMed]
  106. Lu L, Liu D, Ceng X. Corticotropin-releasing factor receptor type 1 mediates stress-induced relapse to cocaine-conditioned place preference in rats. Eur J Pharmacol. 2001;415:203?208. [PubMed]
  107. Lu L, Shepard JD, Hall FS, Shaham Y. Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci Biobehav Rev. 2003;27:457?491. [PubMed]
  108. Makino S, Gold PW, Schulkin J. Corticosterone effects on corticotropin-releasing hormone mRNA in the central nucleus of the amygdala and the parvocellular region of the paraventricular nucleus of the hypothalamus. Brain Res. 1994;640:105?112. [PubMed]
  109. Martin-Fardon R, Ciccocioppo R, Massi M, Weiss F. Nociceptin prevents stress-induced ethanol- but not cocaine-seeking behavior in rats. Neuroreport. 2000;11:1939?1943. [PubMed]
  110. McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ. ΔFosB: a molecular switch for long-term adaptation in the brain. Brain Res Mol Brain Res. 2004;132:146?154. [PubMed]
  111. McLaughlin JP, Marton-Popovici M, Chavkin C. κ Opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J Neurosci. 2003;23:5674?5683. [PMC free article] [PubMed]
  112. Merlo-Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F. 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. 1995;15:5439?5447. [PubMed]
  113. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B, et al. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature. 1995;377:532?535. [PubMed]
  114. Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett. 1994;341:33?38. [PubMed]
  115. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K. Distribution of orexin neurons in the adult rat brain. Brain Res. 1999;827:243?260. [PubMed]
  116. Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T. Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J Neurosci. 2006;26:398?405. [PubMed]
  117. Neal CR, Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Watson SJ., Jr Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol. 1999;406:503?547. [PubMed]
  118. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci. 2005;8:1445?1449. [PubMed]
  119. Neugebauer V, Li W, Bird GC, Han JS. The amygdala and persistent pain. Neuroscientist. 2004;10:221?234. [PubMed]
  120. Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR. Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science. 2004;303:1512?1514. [PubMed]
  121. O?Dell LE, Koob GF. ?Nicotine deprivation effect? in rats with intermittent 23-hour access to intravenous nicotine self-administration. Pharmacol Biochem Behav. 2007;86:346?353. [PMC free article] [PubMed]
  122. O?Dell LE, Roberts AJ, Smith RT, Koob GF. Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure. Alcohol Clin Exp Res. 2004;28:1676?1682. [PubMed]
  123. Olive MF, Koenig HN, Nannini MA, Hodge CW. Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake. Pharmacol Biochem Behav. 2002;72:213?220. [PubMed]
  124. Overstreet DH, Knapp DJ, Breese GR. Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors. Pharmacol Biochem Behav. 2004;77:405?413. [PMC free article] [PubMed]
  125. Pandey SC, Zhang H, Roy A, Xu T. Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest. 2005;115:2762?2773. [PMC free article] [PubMed]
  126. Parker RM, Herzog H. Regional distribution of Y-receptor subtype mRNAs in rat brain. Eur J Neurosci. 1999;11:1431?1448. [PubMed]
  127. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18:9996?10015. [PubMed]
  128. Pfaff D. Brain Arousal and Information Theory: Neural and Genetic Mechanisms. Cambridge, MA: Harvard University Press; 2006.
  129. Pfeiffer A, Brantl V, Herz A, Emrich HM. Psychotomimesis mediated by κ opiate receptors. Science. 1986;233:774?776. [PubMed]
  130. Phelps EA, Le Doux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron. 2005;48:175?187. [PubMed]
  131. Piazza PV, Deroche V, Deminière JM, Maccari S, Le Moal M, Simon H. Corticosterone in the range of stress-induced levels possesses reinforcing properties: implications for sensation-seeking behaviors. Proc Natl Acad Sci USA. 1993;90:11738?11742. [PMC free article] [PubMed]
  132. Piazza PV, Le Moal M. Glucocorticoids as a biological substrate of reward: physiological and pathophysiological implications. Brain Res Brain Res Rev. 1997;25:359?372. [PubMed]
  133. Primeaux SD, Wilson SP, Bray GA, York DA, Wilson MA. Overexpression of neuropeptide Y in the central nucleus of the amygdala decreases ethanol self-administration in ?anxious? rats. Alcohol Clin Exp Res. 2006;30:791?801. [PubMed]
  134. Rainnie DG, Bergeron R, Sajdyk TJ, Patil M, Gehlert DR, Shekhar A. Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. J Neurosci. 2004;24:3471?3479. [PubMed]
  135. Rasmussen DD, Boldt BM, Bryant CA, Mitton DR, Larsen SA, Wilkinson CW. Chronic daily ethanol and withdrawal: 1. Long-term changes in the hypothalamo-pituitary-adrenal axis. Alcohol Clin Exp Res. 2000;24:1836?1849. [PubMed]
  136. Rassnick S, Heinrichs SC, Britton KT, Koob GF. Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res. 1993;605:25?32. [PubMed]
  137. Rattan AK, Koo KL, Tejwani GA, Bhargava HN. The effect of morphine tolerance dependence and abstinence on immunoreactive dynorphin (1?13) levels in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of the rat. Brain Res. 1992;584:207?212. [PubMed]
  138. Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ, Jr, Civelli O. Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science. 1995;270:792?794. [PubMed]
  139. Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenesch JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE. Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA. 2001;98:2843?2848. [PMC free article] [PubMed]
  140. Richardson HN, Zhao Y, Fekete EM, Funk CK, Wirsching P, Janda KD, Zorrilla EP, Koob GF. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist. Pharmacol Biochem Behav. 2008;88:497?510. [PMC free article] [PubMed]
  141. Richter RM, Weiss F. In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse. 1999;32:254?261. [PubMed]
  142. Rimondini R, Arlinde C, Sommer W, Heilig M. Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J. 2002;16:27?35. [PubMed]
  143. Rimondini R, Thorsell A, Heilig M. 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. 2005;375:129?133. [PubMed]
  144. Robbins TW, Everitt BJ. Arousal systems and attention. In: Gazzaniga MS, editor. The Cognitive Neurosciences. Cambridge, MA: MIT Press; 1995. pp. 703?720.
  145. Roberto M, Siggins GR. Nociceptin/orphanin FQ presynaptically decreases GABAergic transmission and blocks the ethanol-induced increase of GABA release in central amygdala. Proc Natl Acad Sci USA. 2006;103:9715?9720. [PMC free article] [PubMed]
  146. Roberto M, Madamba SG, Moore SD, Tallent MK, Siggins GR. Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons. Proc Natl Acad Sci USA. 2003;100:2053?2058. [PMC free article] [PubMed]
  147. Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR. Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci. 2004;24:10159?10166. [PubMed]
  148. Roberts AJ, Heyser CJ, Cole M, Griffin P, Koob GF. Excessive ethanol drinking following a history of dependence: animal model of allostasis. Neuropsychopharmacology. 2000;22:581?594. [PubMed]
  149. Rodriguez de Fonseca F, Carrera MRA, Navarro M, Koob GF, Weiss F. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science. 1997;276:2050?2054. [PubMed]
  150. Rohrer DK, Kobilka BK. Insights from in vivo modification of adrenergic receptor gene expression. Annu Rev Pharmacol Toxicol. 1998;38:351?373. [PubMed]
  151. Romach MK, Sellers EM. Management of the alcohol withdrawal syndrome. Annu Rev Med. 1991;42:323?340. [PubMed]
  152. Roy A, Pandey SC. The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure. Alcohol Clin Exp Res. 2002;26:796?803. [PubMed]
  153. Rudoy CA, van Bockstaele EJ. Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1119?1129. [PubMed]
  154. Sakamoto F, Yamada S, Ueta Y. Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons. Regul Pept. 2004;118:183?191. [PubMed]
  155. Sakoori K, Murphy NP. Endogenous nociceptin (orphanin FQ) suppresses basal hedonic state and acute reward responses to methamphetamine and ethanol, but facilitates chronic responses. Neuropsychopharmacology. 2008;33:877?891. [PubMed]
  156. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573?585. [PubMed]
  157. Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G. Brain corticotropin-releasing factor mediates ?anxiety-like? behavior induced by cocaine withdrawal in rats. Brain Res. 1995;675:89?97. [PubMed]
  158. Schulkin J, McEwen BS, Gold PW. Allostasis, amygdala, and anticipatory angst. Neurosci Biobehav Rev. 1994;18:385?396. [PubMed]
  159. Schulteis G, Stinus L, Risbrough VB, Koob GF. Clonidine blocks acquisition but not expression of conditioned opiate withdrawal in rats. Neuropsychopharmacology. 1998;19:406?416. [PubMed]
  160. Selye H. A syndrome produced by diverse nocuous agents. Nature. 1936;138:32.
  161. Semba J, Wakuta M, Maeda J, Suhara T. Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats: implications for precipitation of depression during smoking cessation. Psychoneuroendocrinology. 2004;29:215?226. [PubMed]
  162. Shaham Y, Funk D, Erb S, Brown TJ, Walker CD, Stewart J. Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci. 1997;17:2605?2614. [PubMed]
  163. Shaham Y, Erb S, Leung S, Buczek Y, Stewart J. CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine-and heroin-trained rats. Psychopharmacology (Berl) 1998;137:184?190. [PubMed]
  164. Shaham Y, Erb S, Stewart J. Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res Brain Res Rev. 2000;33:13?33. [PubMed]
  165. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 2003;168:3?20. [PubMed]
  166. Shalev U, Finnie PS, Quinn T, Tobin S, Wahi P. A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats. Psychopharmacology (Berl) 2006;187:376?384. [PubMed]
  167. Sharp BM, Matta SG. Detection by in vivo microdialysis of nicotine-induced norepinephrine secretion from the hypothalamic paraventricular nucleus of freely moving rats: dose-dependency and desensitization. Endocrinology. 1993;133:11?19. [PubMed]
  168. Shaw-Lutchman TZ, Barrot M, Wallace T, Gilden L, Zachariou V, Impey S, Duman RS, Storm D, Nestler EJ. Regional and cellular mapping of cAMP response element-mediated transcription during naltrex-one-precipitated morphine withdrawal. J Neurosci. 2002;22:3663?3672. [PubMed]
  169. Shepard JD, Barron KW, Myers DA. Corticosterone delivery to the amygdala increases corticotropin-releasing factor mRNA in the central amygdaloid nucleus and anxiety-like behavior. Brain Res. 2000;861:288?295. [PubMed]
  170. Shippenberg TS, Koob GF. Recent advances in animal models of drug addiction and alcoholism. In: Davis KL, Charney D, Coyle JT, Nemeroff C, editors. Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia: Lippincott Williams and Wilkins; 2002. pp. 1381?1397.
  171. Shippenberg TS, Zapata A, Chefer VI. Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther. 2007;116:306?321. [PMC free article] [PubMed]
  172. Shoblock JR, Wichmann J, Maidment NT. The effect of a systemically active ORL-1 agonist, Ro 64?6198, on the acquisition, expression, extinction, and reinstatement of morphine conditioned place preference. Neuropharmacology. 2005;49:439?446. [PubMed]
  173. Solomon RL, Corbit JD. An opponent-process theory of motivation: 1. Temporal dynamics of affect. Psychol Rev. 1974;81:119?145. [PubMed]
  174. Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, Heilig MA. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol Psychiatry. 2008;63:139?145. [PubMed]
  175. Song ZH, Takemori AE. Stimulation by corticotropin-releasing factor of the release of immunoreactive dynorphin A from mouse spinal cords in vitro. Eur J Pharmacol. 1992;222:27?32. [PubMed]
  176. Spangler R, Unterwald EM, Kreek MJ. ?Binge? cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen. Brain Res Mol Brain Res. 1993;19:323?327. [PubMed]
  177. Sparber SB, Meyer DR. Clonidine antagonizes naloxone-induced suppression of conditioned behavior and body weight loss in morphine-dependent rats. Pharmacol Biochem Behav. 1978;9:319?325. [PubMed]
  178. Sparta DR, Fee JR, Hayes DM, Knapp DJ, MacNeil DJ, Thiele TE. Peripheral and central administration of a selective neuropeptide Y Y1 receptor antagonist suppresses ethanol intake by C57BL/6J mice. Alcohol Clin Exp Res. 2004;28:1324?1330. [PMC free article] [PubMed]
  179. Specio SE, Wee S, O?Dell LE, Boutrel B, Zorrilla EP, Koob GF. CRF1 receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology (Berl) 2008;196:473?482. [PMC free article] [PubMed]
  180. Sterling P, Eyer J. Allostasis: a new paradigm to explain arousal pathology. In: Fisher S, Reason J, editors. Handbook of Life Stress, Cognition and Health. Chichiester: John Wiley; 1988. pp. 629?649.
  181. Stinus L, Cador M, Zorrilla EP, Koob GF. Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. Neuropsychopharmacology. 2005;30:90?98. [PubMed]
  182. Sutcliffe JG, de Lecea L. The hypocretins: setting the arousal threshold. Nat Rev Neurosci. 2002;3:339?349. [PubMed]
  183. Suzuki R, Lumeng L, McBride WJ, Li TK, Hwang BH. Reduced neuropeptide Y mRNA expression in the central nucleus of amygdala of alcohol preferring (P) rats: its potential involvement in alcohol preference and anxiety. Brain Res. 2004;1014:251?254. [PubMed]
  184. Swanson LW, Simmons DM. Differential steroid hormone and neural influences on peptide mRNA levels in CRH cells of the paraventricular nucleus: a hybridization histochemical study in the rat. J Comp Neurol. 1989;285:413?435. [PubMed]
  185. Swanson LW, Sawchenko PE, Rivier J, Vale W. The organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology. 1983;36:165?186. [PubMed]
  186. Thiele TE, Koh MT, Pedrazzini T. Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J Neurosci . 2002;22:RC208. [PubMed]
  187. Thiele TE, Naveilhan P, Ernfors P. Assessment of ethanol consumption and water drinking by NPY Y2 receptor knockout mice. Peptides. 2004;25:975?983. [PubMed]
  188. Thorsell A, Rimondini R, Heilig M. Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats. Neurosci Lett. 2002;332:1?4. [PubMed]
  189. Thorsell A, Slawecki CJ, Ehlers CL. Effects of neuropeptide Y and corticotropin-releasing factor on ethanol intake in Wistar rats: interaction with chronic ethanol exposure. Behav Brain Res. 2005;161:133?140. [PubMed]
  190. Thorsell A, Rapunte-Canonigo V, O?Dell L, Chen SA, King A, Lekic D, Koob GF, Sanna PP. Viral vector-induced amygdala NPY over-expression reverses increased alcohol intake caused by repeated deprivations in Wistar rats. Brain. 2007;130:1330?1337. [PMC free article] [PubMed]
  191. Trzaskowska E, Kostowski W. Further studies on the role of noradrenergic mechanisms in ethanol withdrawal syndrome in rats. Pol J Pharmacol Pharm. 1983;35:351?358. [PubMed]
  192. Tucci S, Cheeta S, Seth P, File SE. Corticotropin releasing factor antagonist, α-helical CRF9?41, reverses nicotine-induced conditioned, but not unconditioned, anxiety. Psychopharmacology (Berl) 2003;167:251?256. [PubMed]
  193. Turchan J, Lason W, Budziszewska B, Przewlocka B. Effects of single and repeated morphine administration on the prodynorphin, proenkephalin and dopamine D2 receptor gene expression in the mouse brain. Neuropeptides. 1997;31:24?28. [PubMed]
  194. Turnbull AV, Rivier C. Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides. Proc Soc Exp Biol Med. 1997;215:1?10. [PubMed]
  195. Unterwald EM, Rubenfeld JM, Kreek MJ. Repeated cocaine administration upregulates kappa and mu, but not delta, opioid receptors. Neuroreport. 1994;5:1613?1616. [PubMed]
  196. 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]
  197. Valdez GR, Roberts AJ, Chan K, Davis H, Brennan M, Zorrilla EP, Koob GF. Increased ethanol self-administration and anxiety-like behavior during acute withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol Clin Exp Res. 2002;26:1494?1501. [PubMed]
  198. Valdez GR, Zorrilla EP, Roberts AJ, Koob GF. Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence. Alcohol. 2003;29:55?60. [PubMed]
  199. Valdez GR, Sabino V, Koob GF. Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation. Alcohol Clin Exp Res. 2004;28:865?872. [PubMed]
  200. Valdez GR, Platt DM, Rowlett JK, Rüedi-Bettschen D, Spealman RD. κ Agonist-induced reinstatement of cocaine seeking in squirrel monkeys: a role for opioid and stress-related mechanisms. J Pharmacol Exp Ther. 2007;323:525?533. [PubMed]
  201. Veinante P, Freund-Mercier MJ. Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol. 1997;383:305?325. [PubMed]
  202. Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: Involvement of the orbitofrontal cortex. Cereb Cortex. 2000;10:318?325. [PubMed]
  203. Walker BM, Koob GF. Pharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence. Neuropsychopharmacology. 2008;33:643?652. [PMC free article] [PubMed]
  204. Walker BM, Rasmussen DD, Raskind MA, Koob GF. α1-Noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol. Alcohol Clin Exp Res. 2008;42:91?97. [PMC free article] [PubMed]
  205. Wang X, Cen X, Lu L. Noradrenaline in the bed nucleus of the stria terminalis is critical for stress-induced reactivation of morphine-conditioned place preference in rats. Eur J Pharmacol. 2001;432:153?161. [PubMed]
  206. Wang J, Fang Q, Liu Z, Lu L. Region-specific effects of brain corticotropin-releasing factor receptor type 1 blockade on footshock-stress-or drug-priming-induced reinstatement of morphine conditioned place preference in rats. Psychopharmacology (Berl) 2006;185:19?28. [PubMed]
  207. Wang B, You ZB, Rice KC, Wise RA. Stress-induced relapse to cocaine seeking: roles for the CRF(2) receptor and CRF-binding protein in the ventral tegmental area of the rat. Psychopharmacology (Berl) 2007;193:283?294. [PubMed]
  208. Watanabe T, Nakagawa T, Yamamoto R, Maeda A, Minami M, Satoh M. Involvement of noradrenergic system within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats. Psychopharmacology (Berl) 2003;170:80?88. [PubMed]
  209. Watson SJ, Khachaturian H, Akil H, Coy DH, Goldstein A. Comparison of the distribution of dynorphin systems and enkephalin systems in brain. Science. 1982;218:1134?1136. [PubMed]
  210. Wee S, Mandyam CD, Lekic DM, Koob GF. α1-Noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access. Eur Neuropsychopharmacol. 2008;18:303?311. [PMC free article] [PubMed]
  211. Weiss F, Ciccocioppo R, Parsons LH, Katner S, Liu X, Zorrilla EP, Valdez GR, Ben-Shahar O, Angeletti S, Richter RR. Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors. In: Quinones-Jenab V, editor. The Biological Basis of Cocaine Addiction (series title: Annals of the New York Academy of Sciences, vol 937) New York: New York Academy of Sciences; 2001. pp. 1?26. [PubMed]
  212. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci. 2004;24:11439?11448. [PubMed]
  213. Woldbye DP, Klemp K, Madsen TM. Neuropeptide Y attenuates naloxone-precipitated morphine withdrawal via Y5-like receptors. J Pharmacol Exp Ther. 1998;284:633?636. [PubMed]
  214. Woldbye DP, Ulrichsen J, Haugbol S, Bolwig TG. Ethanol withdrawal in rats is attenuated by intracerebroventricular administration of neuropeptide Y. Alcohol Alcohol. 2002;37:318?321. [PubMed]
  215. Xi ZX, Fuller SA, Stein EA. Dopamine release in the nucleus accumbens during heroin self-administration is modulated by kappa opioid receptors: an in vivo fast-cyclic voltammetry study. J Pharmacol Exp Ther. 1998;284:151?161. [PubMed]
  216. Zhou Y, Leri F, Cummins E, Hoeschele M, Kreek MJ. Involvement of arginine vasopressin and V1b receptor in heroin withdrawal and heroin seeking precipitated by stress and by heroin. Neuropsychopharmacology. 2008;33:226?236. [PubMed]
  217. Zislis G, Desai TV, Prado M, Shah HP, Bruijnzeel AW. Effects of the CRF receptor antagonist D-Phe CRF(12?41) and the α2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats. Neuropharmacology. 2007;53:958?966. [PMC free article] [PubMed]


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