Brain Structure and Function

, Volume 213, Issue 1–2, pp 43–61

Noradrenergic transmission in the extended amygdala: role in increased drug-seeking and relapse during protracted drug abstinence

Review

Abstract

Studies reviewed here implicate the extended amygdala in the negative affective states and increased drug-seeking that occur during protracted abstinence from chronic drug exposure. Norepinephrine (NE) and corticotropin-releasing factor (CRF) signaling in the extended amygdala, including the bed nucleus of the stria terminalis, shell of the nucleus accumbens, and central nucleus of the amygdala, are generally involved in behavioral responses to environmental and internal stressors. Hyperactivity of stress response systems during addiction drives many negative components of drug abstinence. In particular, NE signaling from the nucleus tractus solitarius (NTS) to the extended amygdala, along with increased CRF transmission within the extended amygdala, are critical for the aversiveness of acute opiate withdrawal as well as stress-induced relapse of drug-seeking for opiates, cocaine, ethanol, and nicotine. NE and CRF transmission in the extended amygdala are also implicated in the increased anxiety that occurs during prolonged abstinence from chronic opiates, cocaine, ethanol, and cannabinoids. Many of these stress-associated behaviors are reversed by NE or CRF antagonists given systemically or locally within the extended amygdala. Finally, increased Fos activation in the extended amygdala and NTS is associated with the enhanced preference for drugs and decreased preference for natural rewards observed during protracted abstinence from opiates and cocaine, indicating that these areas are involved in the altered reward processing associated with addiction. Together, these findings suggest that involvement of the extended amygdala and its noradrenergic afferents in anxiety, stress-induced relapse, and altered reward processing reflects a common function for these circuits in stress modulation of drug-seeking.

Keywords

Norepinephrine Withdrawal Anxiety Reinstatement Addiction 

References

  1. Ahmed SH, Walker JR, Koob GF (2000) Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22:413–421. doi:10.1016/S0893-133X(99)00133-5 PubMedGoogle Scholar
  2. Akaoka H, Aston-Jones G (1991) Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input. J Neurosci 11:3830–3839PubMedGoogle Scholar
  3. Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39. doi:10.1016/0306-4522(88)90217-5 PubMedGoogle Scholar
  4. Amit Z, Brown ZW (1982) Actions of drugs of abuse on brain reward systems: a reconsideration with specific attention to alcohol. Pharmacol Biochem Behav 17:233–238. doi:10.1016/0091-3057(82)90075-2 PubMedGoogle Scholar
  5. Amit Z, Brown ZW, Levitan DE, Ogren SO (1977) Noradrenergic mediation of the positive reinforcing properties of ethanol: I. Suppression of ethanol consumption in laboratory rats following dopamine-beta-hydroxylase inhibition. Arch Int Pharmacodyn Ther 230:65–75Google Scholar
  6. Arborelius L, Owens MJ, Plotsky PM, Nemeroff CB (1999) The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 160:1–12. doi:10.1677/joe.0.1600001 PubMedGoogle Scholar
  7. Aston-Jones G, Harris GC (2004) Brain substrates for increased drug seeking during protracted withdrawal. Neuropharmacology 47(Suppl 1):167–179. doi:10.1016/j.neuropharm.2004.06.020 PubMedGoogle Scholar
  8. Aston-Jones G, Rajkowski J, Kubiak P, Akaoka H (1992) Acute morphine induces oscillatory discharge of noradrenergic locus coeruleus neurons in the waking monkey. Neurosci Lett 140:219–224Google Scholar
  9. Aston-Jones G, Shiekhattar R, Akaoka H, Rajkowski J, Kubiak P (1993) Opiates influence locus coeruleus neurons by potent indirect and direct actions. In: Hammer RP Jr (ed) The neurobiology of opiates. CRC Press, Boca Raton, FL, pp 175–202Google Scholar
  10. Aston-Jones G, Hirata H, Akaoka H (1997) Local opiate withdrawal in locus coeruleus in vivo. Brain Res 765:331–336. doi:10.1016/S0006-8993(97)00682-3 PubMedGoogle Scholar
  11. Aston-Jones G, Delfs JM, Druhan J, Zhu Y (1999) The bed nucleus of the stria terminalis. A target site for noradrenergic actions in opiate withdrawal. Ann N Y Acad Sci 877:486–498. doi:10.1111/j.1749-6632.1999.tb09284.x Google Scholar
  12. Aston-Jones G, Mejias-Aponte CA, Waterhouse B (2008) Norepinephrine: CNS Pathways, Neurophysiology. In: Squire L, Albright T, Bloom F, Gage F, Spitzer N (eds) The New Encyclopedia of Neuroscience. Elsevier, San Diego (in press)Google Scholar
  13. Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003) Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464:220–237. doi:10.1002/cne.10783 PubMedGoogle Scholar
  14. Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557. doi:10.1146/annurev.pharmtox.44.101802.121410 PubMedGoogle Scholar
  15. Basso AM, Spina M, Rivier J, Vale W, Koob GF (1999) 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) 145:21–30. doi:10.1007/s002130051028 Google Scholar
  16. Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84. doi:10.1016/S0165-0173(03)00143-7 PubMedGoogle Scholar
  17. Berridge CW, Stratford TL, Foote SL, Kelley AE (1997) Distribution of dopamine beta-hydroxylase-like immunoreactive fibers within the shell subregion of the nucleus accumbens. Synapse 27:230–241. doi:10.1002/(SICI)1098-2396(199711)27:3<230::AID-SYN8>3.0.CO;2-EPubMedGoogle Scholar
  18. Bird SJ, Kuhar MJ (1977) Iontophoretic application of opiates to the locus coeruleus. Brain Res 122:523–533. doi:10.1016/0006-8993(77)90462-0 PubMedGoogle Scholar
  19. Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A (2006) Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49:589–601. doi:10.1016/j.neuron.2006.01.016 PubMedGoogle Scholar
  20. Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF et al (2005) Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci USA 102:19168–19173. doi:10.1073/pnas.0507480102 PubMedGoogle Scholar
  21. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996a) Noradrenergic mechanisms in stress and anxiety: I. Preclinical studies. Synapse 23:28–38. doi:10.1002/(SICI)1098-2396(199605)23:1<28::AID-SYN4>3.0.CO;2-JGoogle Scholar
  22. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996b) Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 23:39–51. doi:10.1002/(SICI)1098-2396(199605)23:1<39::AID-SYN5>3.0.CO;2-IGoogle Scholar
  23. Britton KT, Svensson T, Schwartz J, Bloom FE, Koob GF (1984) Dorsal noradrenergic bundle lesions fail to alter opiate withdrawal or suppression of opiate withdrawal by clonidine. Life Sci 34:133–139. doi:10.1016/0024-3205(84)90583-6 PubMedGoogle Scholar
  24. Caille S, Espejo EF, Reneric JP, Cador M, Koob GF, Stinus L (1999) Total neurochemical lesion of noradrenergic neurons of the locus ceruleus 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 290:881–892PubMedGoogle Scholar
  25. Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob GF et al (2007) Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice. J Neurosci 27:13140–13150. doi:10.1523/JNEUROSCI.2284-07.2007 PubMedGoogle Scholar
  26. Carboni E, Silvagni A (2004) Dopamine reuptake by norepinephrine neurons: exception or rule? Crit Rev Neurobiol 16:121–128. doi:10.1615/CritRevNeurobiol.v16.i12.130 PubMedGoogle Scholar
  27. Carboni E, Silvagni A, Rolando MT, Di Chiara G (2000) Stimulation of in vivo dopamine transmission in the bed nucleus of stria terminalis by reinforcing drugs. J Neurosci 20:RC102Google Scholar
  28. Cecchi M, Khoshbouei H, Javors M, Morilak DA (2002a) Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress. Neuroscience 112:13–21. doi:10.1016/S0306-4522(02)00062-3 PubMedGoogle Scholar
  29. Cecchi M, Khoshbouei H, Morilak DA (2002b) Modulatory effects of norepinephrine, acting on alpha 1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress. Neuropharmacology 43:1139–1147. doi:10.1016/S0028-3908(02)00292-7 PubMedGoogle Scholar
  30. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C et al (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451. doi:10.1016/S0092-8674(00)81973-X PubMedGoogle Scholar
  31. Chieng B, Christie MJ (1995) Lesions to terminals of noradrenergic locus coeruleus neurones do not inhibit opiate withdrawal behaviour in rats. Neurosci Lett 186:37–40. doi:10.1016/0304-3940(95)11276-3 PubMedGoogle Scholar
  32. Childress AR, Ehrman R, McLellan AT, MacRae J, Natale M, O’Brien CP (1994) Can induced moods trigger drug-related responses in opiate abuse patients? J Subst Abuse Treat 11:17–23. doi:10.1016/0740-5472(94)90060-4 PubMedGoogle Scholar
  33. Christie MJ (1991) Mechanisms of opioid actions on neurons of the locus coeruleus. Prog Brain Res 88:197–205. doi:10.1016/S0079-6123(08)63809-1 PubMedGoogle Scholar
  34. Chu K, Koob GF, Cole M, Zorrilla EP, Roberts AJ (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 86:813–821. doi:10.1016/j.pbb.2007.03.009 PubMedGoogle Scholar
  35. Clark MS, Kaiyala KJ (2003) Role of corticotropin-releasing factor family peptides and receptors in stress-related psychiatric disorders. Semin Clin Neuropsychiatry 8:119–136. doi:10.1053/scnp.2003.50011 PubMedGoogle Scholar
  36. Contarino A, Zanotti A, Drago F, Natolino F, Lipartiti M, Giusti P (1997) Conditioned place preference: no tolerance to the rewarding properties of morphine. Naunyn Schmiedebergs Arch Pharmacol 355:589–594. doi:10.1007/PL00004988 PubMedGoogle Scholar
  37. Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K et al (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci USA 96:748–753. doi:10.1073/pnas.96.2.748 PubMedGoogle Scholar
  38. Davis M (1993) Pharmacological analysis of fear-potentiated startle. Braz J Med Biol Res 26:235–260PubMedGoogle Scholar
  39. Davis M (2006) Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am Psychol 61:741–756. doi:10.1037/0003-066X.61.8.741 PubMedGoogle Scholar
  40. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE et al (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95:322–327. doi:10.1073/pnas.95.1.322 PubMedGoogle Scholar
  41. Delfs JM, Zhu Y, Druhan JP, Aston-Jones GS (1998) Origin of noradrenergic afferents to the shell subregion of the nucleus accumbens: anterograde and retrograde tract-tracing studies in the rat. Brain Res 806:127–140. doi:10.1016/S0006-8993(98)00672-6 PubMedGoogle Scholar
  42. Delfs JM, Zhu Y, Druhan JP, Aston-Jones G (2000) Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403:430–434. doi:10.1038/35000212 PubMedGoogle Scholar
  43. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114. doi:10.1016/S0166-4328(02)00286-3 PubMedGoogle Scholar
  44. Diana M, Pistis M, Muntoni A, Rossetti ZL, Gessa G (1992) Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats. Eur J Pharmacol 221:403–404. doi:10.1016/0014-2999(92)90734-L PubMedGoogle Scholar
  45. Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci USA 90:7966–7969. doi:10.1073/pnas.90.17.7966 PubMedGoogle Scholar
  46. Diana M, Pistis M, Muntoni A, Gessa G (1995) Profound decrease of mesolimbic dopaminergic neuronal activity in morphine withdrawn rats. J Pharmacol Exp Ther 272:781–785PubMedGoogle Scholar
  47. Diana M, Pistis M, Muntoni A, Gessa G (1996) Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience 71:411–415. doi:10.1016/0306-4522(95)00482-3 PubMedGoogle Scholar
  48. Diana M, Melis M, Muntoni AL, Gessa GL (1998) Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proc Natl Acad Sci USA 95:10269–10273. doi:10.1073/pnas.95.17.10269 PubMedGoogle Scholar
  49. Diana M, Muntoni AL, Pistis M, Melis M, Gessa GL (1999) Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal. Eur J NeuroSci 11:1037–1041. doi:10.1046/j.1460-9568.1999.00488.x PubMedGoogle Scholar
  50. Dumont EC, Williams JT (2004) Noradrenaline triggers GABAA inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area. J Neurosci 24:8198–8204. doi:10.1523/JNEUROSCI.0425-04.2004 PubMedGoogle Scholar
  51. Dunn AJ, Swiergiel AH (2008) The role of corticotropin-releasing factor and noradrenaline in stress-related responses, and the inter-relationships between the two systems. Eur J Pharmacol 583:186–193. doi:10.1016/j.ejphar.2007.11.069 PubMedGoogle Scholar
  52. Dunn AJ, Swiergiel AH, Palamarchouk V (2004) Brain circuits involved in corticotropin-releasing factor-norepinephrine interactions during stress. Ann N Y Acad Sci 1018:25–34. doi:10.1196/annals.1296.003 PubMedGoogle Scholar
  53. Egli RE, Kash TL, Choo K, Savchenko V, Matthews RT, Blakely RD et al (2005) Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis. Neuropsychopharmacology 30:657–668PubMedGoogle Scholar
  54. Erb S, Stewart J (1999) 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 19:RC35Google Scholar
  55. Erb S, Shaham Y, Stewart J (1998) The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats. J Neurosci 18:5529–5536PubMedGoogle Scholar
  56. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J (2000) Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology 23:138–150. doi:10.1016/S0893-133X(99)00158-X PubMedGoogle Scholar
  57. Erb S, Salmaso N, Rodaros D, Stewart J (2001) 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) 158:360–365. doi:10.1007/s002130000642 Google Scholar
  58. Fibiger HC, Phillips AG (1986) Reward, motivation, cognition: psychobiology of mesotelencephalic dopamine systems. In: Mountcastle VB, Bloom FE, Geiger SR (eds) Handbook of physiology, Sect. 1: The nervous system, vol 4. American Physiological Society, Bethesda, MD, pp 647–675Google Scholar
  59. File SE (1990) New strategies in the search for anxiolytics. Drug Deliv 5:195–201Google Scholar
  60. Forray MI, Bustos G, Gysling K (1999) Noradrenaline inhibits glutamate release in the rat bed nucleus of the stria terminalis: in vivo microdialysis studies. J Neurosci Res 55:311–320. doi:10.1002/(SICI)1097-4547(19990201)55:3<311::AID-JNR6>3.0.CO;2-EPubMedGoogle Scholar
  61. Fox HC, Talih M, Malison R, Anderson GM, Kreek MJ, Sinha R (2005) Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues. Psychoneuroendocrinology 30:880–891. doi:10.1016/j.psyneuen.2005.05.002 PubMedGoogle Scholar
  62. Fox HC, Bergquist KL, Hong KI, Sinha R (2007) Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals. Alcohol Clin Exp Res 31:395–403. doi:10.1111/j.1530-0277.2006.00320.x PubMedGoogle Scholar
  63. Freedman LJ, Cassell MD (1994) Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Res 633:243–252. doi:10.1016/0006-8993(94)91545-8 PubMedGoogle Scholar
  64. Fuentealba JA, Forray MI, Gysling K (2000) Chronic morphine treatment and withdrawal increase extracellular levels of norepinephrine in the rat bed nucleus of the stria terminalis. J Neurochem 75:741–748. doi:10.1046/j.1471-4159.2000.0750741.x PubMedGoogle Scholar
  65. Funk CK, O’Dell LE, Crawford EF, Koob GF (2006) Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 26:11324–11332. doi:10.1523/JNEUROSCI.3096-06.2006 PubMedGoogle Scholar
  66. Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF (2007) Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol Psychiatry 61:78–86. doi:10.1016/j.biopsych.2006.03.063 PubMedGoogle Scholar
  67. Georges F, Aston-Jones G (2001) Potent regulation of midbrain dopamine neurons by the bed nucleus of the stria terminalis. J Neurosci 21:RC160Google Scholar
  68. Georges F, Aston-Jones G (2002) Activation of ventral tegmental area cells by the bed nucleus of the stria terminalis: a novel excitatory amino acid input to midbrain dopamine neurons. J Neurosci 22:5173–5187PubMedGoogle Scholar
  69. Georges F, Aston-Jones G (2003) Prolonged activation of mesolimbic dopaminergic neurons by morphine withdrawal following clonidine: participation of imidazoline and norepinephrine receptors. Neuropsychopharmacology 28:1140–1149PubMedGoogle Scholar
  70. Georgescu D, Zachariou V, Barrot M, Mieda M, Willie JT, Eisch AJ et al (2003) Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. J Neurosci 23:3106–3111PubMedGoogle Scholar
  71. Gewirtz JC, McNish KA, Davis M (1998) Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle. Prog Neuropsychopharmacol Biol Psychiatry 22:625–648. doi:10.1016/S0278-5846(98)00028-1 PubMedGoogle Scholar
  72. Goeders NE (1997) A neuroendocrine role in cocaine reinforcement. Psychoneuroendocrinology 22:237–259. doi:10.1016/S0306-4530(97)00027-9 PubMedGoogle Scholar
  73. Goeders NE (2003) The impact of stress on addiction. Eur Neuropsychopharmacol 13:435–441. doi:10.1016/j.euroneuro.2003.08.004 PubMedGoogle Scholar
  74. Gold MS, Redmond DE Jr, Kleber HD (1978) Clonidine blocks acute opiate-withdrawal symptoms. Lancet 2:599–602. doi:10.1016/S0140-6736(78)92823-4 PubMedGoogle Scholar
  75. Gracy KN, Dankiewicz LA, Koob GF (2001) Opiate withdrawal-induced fos immunoreactivity in the rat extended amygdala parallels the development of conditioned place aversion. Neuropsychopharmacology 24:152–160. doi:10.1016/S0893-133X(00)00186-X PubMedGoogle Scholar
  76. Hamlin AS, Buller KM, Day TA, Osborne PB (2004) Effect of naloxone-precipitated morphine withdrawal on c-fos expression in rat corticotropin-releasing hormone neurons in the paraventricular hypothalamus and extended amygdala. Neurosci Lett 362:39–43. doi:10.1016/j.neulet.2004.02.033 PubMedGoogle Scholar
  77. Harris GC, Aston-Jones G (1993a) Beta-adrenergic antagonists attenuate somatic and aversive signs of opiate withdrawal. Neuropsychopharmacology 9:303–311PubMedGoogle Scholar
  78. Harris GC, Aston-Jones G (1993b) Beta-adrenergic antagonists attenuate withdrawal anxiety in cocaine- and morphine-dependent rats. Psychopharmacology (Berl) 113:131–136. doi:10.1007/BF02244345 Google Scholar
  79. Harris GC, Aston-Jones G (1994) Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature 371:155–157. doi:10.1038/371155a0 PubMedGoogle Scholar
  80. Harris GC, Aston-Jones G (2001) Augmented accumbal serotonin levels decrease the preference for a morphine associated environment during withdrawal. Neuropsychopharmacology 24:75–85. doi:10.1016/S0893-133X(00)00184-6 PubMedGoogle Scholar
  81. Harris GC, Aston-Jones G (2003a) Altered motivation and learning following opiate withdrawal: evidence for prolonged dysregulation of reward processing. Neuropsychopharmacology 28:865–871. doi:10.1038/sj.npp.1300122 PubMedGoogle Scholar
  82. Harris GC, Aston-Jones G (2003b) Enhanced morphine preference following prolonged abstinence: association with increased Fos expression in the extended amygdala. Neuropsychopharmacology 28:292–299. doi:10.1038/sj.npp.1300037 PubMedGoogle Scholar
  83. Harris GC, Aston-Jones G (2006) Arousal and reward: a dichotomy in orexin function. Trends Neurosci 29:571–577. doi:10.1016/j.tins.2006.08.002 PubMedGoogle Scholar
  84. Harris GC, Aston-Jones G (2007) Activation in extended amygdala corresponds to altered hedonic processing during protracted morphine withdrawal. Behav Brain Res 176:251–258. doi:10.1016/j.bbr.2006.10.012 PubMedGoogle Scholar
  85. Harris GC, Altomare K, Aston-Jones G (2001) Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats. Psychopharmacology (Berl) 156:14–22. doi:10.1007/s002130100693 Google Scholar
  86. Harris GC, Wimmer M, Aston-Jones G (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437:556–559. doi:10.1038/nature04071 PubMedGoogle Scholar
  87. Harris GC, Hummel M, Wimmer M, Mague SD, Aston-Jones G (2007) Elevations of FosB in the nucleus accumbens during forced cocaine abstinence correlate with divergent changes in reward function. Neuroscience 147:583–591. doi:10.1016/j.neuroscience.2007.04.050 PubMedGoogle Scholar
  88. Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125. doi:10.1016/0306-4522(91)90202-Y PubMedGoogle Scholar
  89. Heimer L, Alheid GF, Zahm DS (1993) Basal forebrain organization: An anatomical framework for motor aspects of drive and motivation. In: Kalivas PW, Barnes CD (eds) Limbic Motor Circuits and Neuropsychiatry. CRC Press, Boca Raton, pp 1–43Google Scholar
  90. Heinrichs SC, Koob GF (2004) Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther 311:427–440. doi:10.1124/jpet.103.052092 PubMedGoogle Scholar
  91. Heinrichs SC, Menzaghi F, Schulteis G, Koob GF, Stinus L (1995) Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav Pharmacol 6:74–80. doi:10.1097/00008877-199501000-00011 PubMedGoogle Scholar
  92. Hervieu GJ, Cluderay JE, Harrison DC, Roberts JC, Leslie RA (2001) Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience 103:777–797. doi:10.1016/S0306-4522(01)00033-1 PubMedGoogle Scholar
  93. Hnasko TS, Sotak BN, Palmiter RD (2005) Morphine reward in dopamine-deficient mice. Nature 438:854–857. doi:10.1038/nature04172 PubMedGoogle Scholar
  94. Hnasko TS, Sotak BN, Palmiter RD (2007) Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin. J Neurosci 27:12484–12488. doi:10.1523/JNEUROSCI.3133-07.2007 PubMedGoogle Scholar
  95. Hornby PJ, Piekut DT (1989) Opiocortin and catecholamine input to CRF-immunoreactive neurons in rat forebrain. Peptides 10:1139–1146. doi:10.1016/0196-9781(89)90005-3 PubMedGoogle Scholar
  96. Hyman SM, Fox H, Hong KI, Doebrick C, Sinha R (2007) Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment. Exp Clin Psychopharmacol 15:134–143. doi:10.1037/1064-1297.15.2.134 PubMedGoogle Scholar
  97. Ivanov A, Aston-Jones G (2001) Local opiate withdrawal in locus coeruleus neurons in vitro. J Neurophysiol 85:2388–2397PubMedGoogle Scholar
  98. Jasmin L, Narasaiah M, Tien D (2006) Noradrenaline is necessary for the hedonic properties of addictive drugs. Vascul Pharmacol 45:243–250. doi:10.1016/j.vph.2005.08.030 PubMedGoogle Scholar
  99. Kayaba Y, Nakamura A, Kasuya Y, Ohuchi T, Yanagisawa M, Komuro I et al (2003) Attenuated defense response and low basal blood pressure in orexin knockout mice. Am J Physiol Regul Integr Comp Physiol 285:R581–R593PubMedGoogle Scholar
  100. Koob GF (1999a) Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry 46:1167–1180. doi:10.1016/S0006-3223(99)00164-X PubMedGoogle Scholar
  101. Koob GF (1999b) The role of the striatopallidal and extended amygdala systems in drug addiction. Ann N Y Acad Sci 877:445–460. doi:10.1111/j.1749-6632.1999.tb09282.x PubMedGoogle Scholar
  102. Koob GF (1999c) Stress, corticotropin-releasing factor, and drug addiction. Ann N Y Acad Sci 897:27–45. doi:10.1111/j.1749-6632.1999.tb07876.x PubMedGoogle Scholar
  103. Koob GF (2003) Neuroadaptive mechanisms of addiction: studies on the extended amygdala. Eur Neuropsychopharmacol 13:442–452. doi:10.1016/j.euroneuro.2003.08.005 PubMedGoogle Scholar
  104. Koob GF, Heinrichs SC (1999) A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 848:141–152. doi:10.1016/S0006-8993(99)01991-5 PubMedGoogle Scholar
  105. Koob G, Kreek MJ (2007) Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry 164:1149–1159. doi:10.1176/appi.ajp.2007.05030503 PubMedGoogle Scholar
  106. Koob GF, Robledo P, Markou A, Caine SB (1993) The mesocorticolimbic circuit in drug dependence and reward–a role for the extended amygdala? In: Kalivas PW, Barnes CD (eds) Limbic motor circuits and neuropsychiatry. CRC Press, Boca Raton, pp 289–309Google Scholar
  107. Korf J, Bunney BS, Aghajanian GK (1974) Noradrenergic neurons: morphine inhibition of spontaneous activity. Eur J Pharmacol 25:165–169. doi:10.1016/0014-2999(74)90045-4 PubMedGoogle Scholar
  108. Kosten TA (1994) Clonidine attenuates conditioned aversion produced by naloxone-precipitated opiate withdrawal. Eur J Pharmacol 254:59–63. doi:10.1016/0014-2999(94)90370-0 PubMedGoogle Scholar
  109. Kosten TR, Rounsaville BJ, Kleber HD (1986) A 2.5-year follow-up of depression, life crises, and treatment effects on abstinence among opioid addicts. Arch Gen Psychiatry 43:733–738PubMedGoogle Scholar
  110. Laviolette SR, Nader K, van der Kooy D (2002) Motivational state determines the functional role of the mesolimbic dopamine system in the mediation of opiate reward processes. Behav Brain Res 129:17–29. doi:10.1016/S0166-4328(01)00327-8 PubMedGoogle Scholar
  111. Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B (2006) The orexin system regulates alcohol-seeking in rats. Br J Pharmacol 148:752–759. doi:10.1038/sj.bjp.0706789 PubMedGoogle Scholar
  112. Le AD, Harding S, Juzytsch W, Watchus J, Shalev U, Shaham Y (2000) The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats. Psychopharmacology (Berl) 150:317–324. doi:10.1007/s002130000411 Google Scholar
  113. Le AD, Harding S, Juzytsch W, Funk D, Shaham Y (2005) Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats. Psychopharmacology (Berl) 179:366–373. doi:10.1007/s00213-004-2036-y Google Scholar
  114. Lee Y, Davis M (1997) Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex. J Neurosci 17:6434–6446PubMedGoogle Scholar
  115. Leri F, Flores J, Rodaros D, Stewart J (2002) 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 22:5713–5718PubMedGoogle Scholar
  116. Lett BT (1989) Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine. Psychopharmacology (Berl) 98:357–362. doi:10.1007/BF00451687 Google Scholar
  117. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X et al (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–376. doi:10.1016/S0092-8674(00)81965-0 PubMedGoogle Scholar
  118. Liu X, Weiss F (2002) 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 22:7856–7861PubMedGoogle Scholar
  119. Lu L, Ceng X, Huang M (2000) Corticotropin-releasing factor receptor type I mediates stress-induced relapse to opiate dependence in rats. NeuroReport 11:2373–2378PubMedCrossRefGoogle Scholar
  120. Lu L, Shepard JD, Scott Hall F, Shaham Y (2003) Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci Biobehav Rev 27:457–491. doi:10.1016/S0149-7634(03)00073-3 PubMedGoogle Scholar
  121. Lu L, Chen H, Su W, Ge X, Yue W, Su F et al (2005) Role of withdrawal in reinstatement of morphine-conditioned place preference. Psychopharmacology (Berl) 181:90–100. doi:10.1007/s00213-005-2207-5 Google Scholar
  122. Maldonado R (1997) Participation of noradrenergic pathways in the expression of opiate withdrawal: biochemical and pharmacological evidence. Neurosci Biobehav Rev 21:91–104. doi:10.1016/0149-7634(95)00061-5 PubMedGoogle Scholar
  123. Mantsch JR, Baker DA, Francis DM, Katz ES, Hoks MA, Serge JP (2008) Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats. Psychopharmacology (Berl) 195:591–603. doi:10.1007/s00213-007-0950-5 Google Scholar
  124. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M et al (2001) Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435:6–25. doi:10.1002/cne.1190 PubMedGoogle Scholar
  125. Mason ST, Corcoran ME, Fibiger HC (1979) Noradrenaline and ethanol intake in the rat. Neurosci Lett 12:137–142. doi:10.1016/0304-3940(79)91494-0 PubMedGoogle Scholar
  126. Mateo Y, Lack CM, Morgan D, Roberts DC, Jones SR (2005) Reduced dopamine terminal function and insensitivity to cocaine following cocaine binge self-administration and deprivation. Neuropsychopharmacology 30:1455–1463. doi:10.1038/sj.npp.1300687 PubMedGoogle Scholar
  127. McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ (2004) DeltaFosB: a molecular switch for long-term adaptation in the brain. Brain Res Mol Brain Res 132:146–154. doi:10.1016/j.molbrainres.2004.05.014 PubMedGoogle Scholar
  128. McFarland K, Davidge SB, Lapish CC, Kalivas PW (2004) Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior. J Neurosci 24:1551–1560. doi:10.1523/JNEUROSCI.4177-03.2004 PubMedGoogle Scholar
  129. Merlo Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF et al (1995) 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 15:5439–5447PubMedGoogle Scholar
  130. Morilak DA, Barrera G, Echevarria DJ, Garcia AS, Hernandez A, Ma S et al (2005) Role of brain norepinephrine in the behavioral response to stress. Prog Neuropsychopharmacol Biol Psychiatry 29:1214–1224. doi:10.1016/j.pnpbp.2005.08.007 PubMedGoogle Scholar
  131. Nader K, van der Kooy D (1996) Clonidine antagonizes the aversive effects of opiate withdrawal and the rewarding effects of morphine only in opiate withdrawn rats. Behav Neurosci 110:389–400. doi:10.1037/0735-7044.110.2.389 PubMedGoogle Scholar
  132. Nakagawa T, Yamamoto R, Fujio M, Suzuki Y, Minami M, Satoh M et al (2005) Involvement of the bed nucleus of the stria terminalis activated by the central nucleus of the amygdala in the negative affective component of morphine withdrawal in rats. Neuroscience 134:9–19. doi:10.1016/j.neuroscience.2005.03.029 PubMedGoogle Scholar
  133. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K (1999) Distribution of orexin neurons in the adult rat brain. Brain Res 827:243–260. doi:10.1016/S0006-8993(99)01336-0 PubMedGoogle Scholar
  134. Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M et al (2006) Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J Neurosci 26:398–405. doi:10.1523/JNEUROSCI.2761-05.2006 PubMedGoogle Scholar
  135. Newman-Tancredi A, Audinot-Bouchez V, Gobert A, Millan MJ (1997) Noradrenaline and adrenaline are high affinity agonists at dopamine D4 receptors. Eur J Pharmacol 319:379–383. doi:10.1016/S0014-2999(96)00985-5 PubMedGoogle Scholar
  136. Nishino S (2007) Narcolepsy: pathophysiology and pharmacology. J Clin Psychiatry 68(Suppl 13):9–15PubMedGoogle Scholar
  137. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355:39–40. doi:10.1016/S0140-6736(99)05582-8 PubMedGoogle Scholar
  138. O’Brien CP (1997) A range of research-based pharmacotherapies for addiction. Science 278:66–70. doi:10.1126/science.278.5335.66 PubMedGoogle Scholar
  139. Olson VG, Heusner CL, Bland RJ, During MJ, Weinshenker D, Palmiter RD (2006) Role of noradrenergic signaling by the nucleus tractus solitarius in mediating opiate reward. Science 311:1017–1020. doi:10.1126/science.1119311 PubMedGoogle Scholar
  140. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167. doi:10.1016/0165-0270(85)90031-7 PubMedGoogle Scholar
  141. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG et al (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015PubMedGoogle Scholar
  142. Phelix CF, Liposits Z, Paull WK (1992) Monoamine innervation of bed nucleus of stria terminalis: an electron microscopic investigation. Brain Res Bull 28:949–965. doi:10.1016/0361-9230(92)90218-M PubMedGoogle Scholar
  143. Phelix CF, Liposits Z, Paull WK (1994) Catecholamine-CRF synaptic interaction in a septal bed nucleus: afferents of neurons in the bed nucleus of the stria terminalis. Brain Res Bull 33:109–119. doi:10.1016/0361-9230(94)90056-6 PubMedGoogle Scholar
  144. Phelps EA, LeDoux JE (2005) Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48:175–187. doi:10.1016/j.neuron.2005.09.025 PubMedGoogle Scholar
  145. Piazza PV, Le Moal ML (1996) Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons. Annu Rev Pharmacol Toxicol 36:359–378. doi:10.1146/annurev.pa.36.040196.002043 PubMedGoogle Scholar
  146. Pothos E, Rada P, Mark GP, Hoebel BG (1991) Dopamine microdialysis in the nucleus accumbens during acute and chronic morphine, naloxone-precipitated withdrawal and clonidine treatment. Brain Res 566:348–350. doi:10.1016/0006-8993(91)91724-F PubMedGoogle Scholar
  147. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3–33. doi:10.1016/S0014-2999(03)01272-X PubMedGoogle Scholar
  148. Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ (1990) Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 10:2308–2317PubMedGoogle Scholar
  149. Rasmussen DD, Mitton DR, Green J, Puchalski S (2001) Chronic daily ethanol and withdrawal: 2. Behavioral changes during prolonged abstinence. Alcohol Clin Exp Res 25:999–1005. doi:10.1111/j.1530-0277.2001.tb02308.x Google Scholar
  150. Rassnick S, Heinrichs SC, Britton KT, Koob GF (1993a) Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res 605:25–32. doi:10.1016/0006-8993(93)91352-S PubMedGoogle Scholar
  151. Rassnick S, Stinus L, Koob GF (1993b) The effects of 6-hydroxydopamine lesions of the nucleus accumbens and the mesolimbic dopamine system on oral self-administration of ethanol in the rat. Brain Res 623:16–24. doi:10.1016/0006-8993(93)90004-7 PubMedGoogle Scholar
  152. Richter RM, Weiss F (1999) In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 32:254–261PubMedGoogle Scholar
  153. Risbrough VB, Stein MB (2006) Role of corticotropin releasing factor in anxiety disorders: a translational research perspective. Horm Behav 50:550–561. doi:10.1016/j.yhbeh.2006.06.019 PubMedGoogle Scholar
  154. Rodaros D, Caruana DA, Amir S, Stewart J (2007) Corticotropin-releasing factor projections from limbic forebrain and paraventricular nucleus of the hypothalamus to the region of the ventral tegmental area. Neuroscience 150:8–13. doi:10.1016/j.neuroscience.2007.09.043 PubMedGoogle Scholar
  155. Rodgers RJ (1997) Animal models of ‘anxiety’: where next? Behav Pharmacol 8:477–496; discussion 497–504. doi:10.1097/00008877-199711000-00003 Google Scholar
  156. Rodriguez de Fonseca F, Carrera MR, Navarro M, Koob GF, Weiss F (1997) Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 276:2050–2054. doi:10.1126/science.276.5321.2050 PubMedGoogle Scholar
  157. Rossetti ZL, Melis F, Carboni S, Diana M, Gessa GL (1992) Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine. Alcohol Clin Exp Res 16:529–532. doi:10.1111/j.1530-0277.1992.tb01411.x PubMedGoogle Scholar
  158. Sakamoto F, Yamada S, Ueta Y (2004) 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 118:183–191. doi:10.1016/j.regpep.2003.12.014 PubMedGoogle Scholar
  159. Sakanaka M, Shibasaki T, Lederis K (1986) Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex. Brain Res 382:213–238. doi:10.1016/0006-8993(86)91332-6 PubMedGoogle Scholar
  160. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H et al (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585. doi:10.1016/S0092-8674(00)80949-6 PubMedGoogle Scholar
  161. Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y et al (2005) Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron 46:297–308. doi:10.1016/j.neuron.2005.03.010 PubMedGoogle Scholar
  162. Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G (1995) Brain corticotropin-releasing factor mediates ‘anxiety-like’ behavior induced by cocaine withdrawal in rats. Brain Res 675:89–97. doi:10.1016/0006-8993(95)00043-P PubMedGoogle Scholar
  163. Sarnyai Z, Shaham Y, Heinrichs SC (2001) The role of corticotropin-releasing factor in drug addiction. Pharmacol Rev 53:209–243PubMedGoogle Scholar
  164. Schank JR, Ventura R, Puglisi-Allegra S, Alcaro A, Cole CD, Liles LC et al (2006) Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. Neuropsychopharmacology 31:2221–2230PubMedGoogle Scholar
  165. Shaham Y, Stewart J (1995) Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal. Psychopharmacology (Berl) 119:334–341. doi:10.1007/BF02246300 Google Scholar
  166. Shaham Y, Rajabi H, Stewart J (1996) Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal. J Neurosci 16:1957–1963PubMedGoogle Scholar
  167. Shaham Y, Funk D, Erb S, Brown TJ, Walker CD, Stewart J (1997) Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 17:2605–2614PubMedGoogle Scholar
  168. Shaham Y, Erb S, Leung S, Buczek Y, Stewart J (1998) 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) 137:184–190. doi:10.1007/s002130050608 Google Scholar
  169. Shaham Y, Erb S, Stewart J (2000a) Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res Brain Res Rev 33:13–33. doi:10.1016/S0165-0173(00)00024-2 PubMedGoogle Scholar
  170. Shaham Y, Highfield D, Delfs J, Leung S, Stewart J (2000b) Clonidine blocks stress-induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons. Eur J NeuroSci 12:292–302. doi:10.1046/j.1460-9568.2000.00899.x PubMedGoogle Scholar
  171. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20. doi:10.1007/s00213-002-1224-x Google Scholar
  172. Shalev U, Morales M, Hope B, Yap J, Shaham Y (2001) Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats. Psychopharmacology (Berl) 156:98–107. doi:10.1007/s002130100748 Google Scholar
  173. Shippenberg TS, Heidbreder C (1995) Sensitization to the conditioned rewarding effects of cocaine: pharmacological and temporal characteristics. J Pharmacol Exp Ther 273:808–815PubMedGoogle Scholar
  174. Siegel JM (2004) Hypocretin (orexin): role in normal behavior and neuropathology. Annu Rev Psychol 55:125–148. doi:10.1146/annurev.psych.55.090902.141545 PubMedGoogle Scholar
  175. Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158:343–359. doi:10.1007/s002130100917 Google Scholar
  176. Sinha R (2007) The role of stress in addiction relapse. Curr Psychiatry Rep 9:388–395. doi:10.1007/s11920-007-0050-6 PubMedGoogle Scholar
  177. Sinha R, Catapano D, O’Malley S (1999) Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology (Berl) 142:343–351. doi:10.1007/s002130050898 Google Scholar
  178. Sinha R, Talih M, Malison R, Cooney N, Anderson GM, Kreek MJ (2003) Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl) 170:62–72. doi:10.1007/s00213-003-1525-8 Google Scholar
  179. Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ (2006) Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatry 63:324–331. doi:10.1001/archpsyc.63.3.324 PubMedGoogle Scholar
  180. Smith RJ, Harris GC, Aston-Jones G (2004) Dependence prior to, but not subsequent to, stimulus-drug conditioning increases drug seeking during protracted morphine withdrawal. Program No. 576.13. 2004 Abstract Viewer and Itinerary Planner. Online. Society for Neuroscience, San Diego, CAGoogle Scholar
  181. Southwick SM, Bremner JD, Rasmusson A, Morgan CA 3rd, Arnsten A, Charney DS (1999) Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry 46:1192–1204. doi:10.1016/S0006-3223(99)00219-X PubMedGoogle Scholar
  182. Spanagel R, Almeida OF, Bartl C, Shippenberg TS (1994) Endogenous kappa-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release. Psychopharmacology (Berl) 115:121–127. doi:10.1007/BF02244761 Google Scholar
  183. Specio SE, Wee S, O’Dell LE, Boutrel B, Zorrilla EP, Koob GF (2007) CRF(1) receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology (Berl). doi:10.1007/s00213-007-0983-9
  184. Stinus L, Cador M, Zorrilla EP, Koob GF (2005) Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. Neuropsychopharmacology 30:90–98. doi:10.1038/sj.npp.1300487 PubMedGoogle Scholar
  185. Stornetta RL, Norton FE, Guyenet PG (1993) Autonomic areas of rat brain exhibit increased Fos-like immunoreactivity during opiate withdrawal in rats. Brain Res 624:19–28. doi:10.1016/0006-8993(93)90055-R PubMedGoogle Scholar
  186. Strawn JR, Geracioti TD Jr (2008) Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety 25:260–271. doi:10.1002/da.20292 PubMedGoogle Scholar
  187. Sutcliffe JG, de Lecea L (2002) The hypocretins: setting the arousal threshold. Nat Rev Neurosci 3:339–349. doi:10.1038/nrn808 PubMedGoogle Scholar
  188. Swiergiel AH, Takahashi LK, Kalin NH (1993) Attenuation of stress-induced behavior by antagonism of corticotropin-releasing factor receptors in the central amygdala in the rat. Brain Res 623:229–234. doi:10.1016/0006-8993(93)91432-R PubMedGoogle Scholar
  189. Treit D, Pinel JP, Fibiger HC (1981) Conditioned defensive burying: a new paradigm for the study of anxiolytic agents. Pharmacol Biochem Behav 15:619–626. doi:10.1016/0091-3057(81)90219-7 PubMedGoogle Scholar
  190. Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438:71–75. doi:10.1016/S0014-5793(98)01266-6 PubMedGoogle Scholar
  191. Valdez GR, Roberts AJ, Chan K, Davis H, Brennan M, Zorrilla EP et al (2002) Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol Clin Exp Res 26:1494–1501PubMedGoogle Scholar
  192. Valdez GR, Zorrilla EP, Roberts AJ, Koob GF (2003) Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence. Alcohol 29:55–60. doi:10.1016/S0741-8329(03)00020-X PubMedGoogle Scholar
  193. Veinante P, Stoeckel ME, Lasbennes F, Freund-Mercier MJ (2003) c-Fos and peptide immunoreactivities in the central extended amygdala of morphine-dependent rats after naloxone-precipitated withdrawal. Eur J NeuroSci 18:1295–1305. doi:10.1046/j.1460-9568.2003.02837.x PubMedGoogle Scholar
  194. Walker DL, Davis M (1997) Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. J Neurosci 17:9375–9383PubMedGoogle Scholar
  195. Walker DL, Toufexis DJ, Davis M (2003) Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol 463:199–216. doi:10.1016/S0014-2999(03)01282-2 PubMedGoogle Scholar
  196. Walters CL, Aston-Jones G, Druhan JP (2000) Expression of fos-related antigens in the nucleus accumbens during opiate withdrawal and their attenuation by a D2 dopamine receptor agonist. Neuropsychopharmacology 23:307–315. doi:10.1016/S0893-133X(00)00113-5 PubMedGoogle Scholar
  197. Wang X, Cen X, Lu L (2001) 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 432:153–161. doi:10.1016/S0014-2999(01)01487-X PubMedGoogle Scholar
  198. Wang B, Shaham Y, Zitzman D, Azari S, Wise RA, You ZB (2005) Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking. J Neurosci 25:5389–5396. doi:10.1523/JNEUROSCI.0955-05.2005 PubMedGoogle Scholar
  199. Wang J, Fang Q, Liu Z, Lu L (2006) 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) 185:19–28. doi:10.1007/s00213-005-0262-6 Google Scholar
  200. Wang B, You ZB, Rice KC, Wise RA (2007) 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) 193:283–294. doi:10.1007/s00213-007-0782-3 Google Scholar
  201. Watanabe T, Nakagawa T, Yamamoto R, Maeda A, Minami M, Satoh M (2003) Involvement of noradrenergic system within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats. Psychopharmacology (Berl) 170:80–88. doi:10.1007/s00213-003-1504-0 Google Scholar
  202. Weinshenker D, Schroeder JP (2007) There and back again: a tale of norepinephrine and drug addiction. Neuropsychopharmacology 32:1433–1451. doi:10.1038/sj.npp.1301263 PubMedGoogle Scholar
  203. Weinshenker D, Rust NC, Miller NS, Palmiter RD (2000) Ethanol-associated behaviors of mice lacking norepinephrine. J Neurosci 20:3157–3164PubMedGoogle Scholar
  204. Weiss F, Ciccocioppo R, Parsons LH, Katner S, Liu X, Zorrilla EP et al (2001) Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors. Ann N Y Acad Sci 937:1–26PubMedGoogle Scholar
  205. Willie JT, Chemelli RM, Sinton CM, Yanagisawa M (2001) To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci 24:429–458. doi:10.1146/annurev.neuro.24.1.429 PubMedGoogle Scholar
  206. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T et al (2004) Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci 24:11439–11448. doi:10.1523/JNEUROSCI.3459-04.2004 PubMedGoogle Scholar
  207. Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215–247. doi:10.1016/0006-8993(78)90253-6 PubMedGoogle Scholar
  208. Wise RA (1996) Neurobiology of addiction. Curr Opin Neurobiol 6:243–251. doi:10.1016/S0959-4388(96)80079-1 PubMedGoogle Scholar
  209. Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494. doi:10.1038/nrn1406 PubMedGoogle Scholar
  210. Yoshida K, McCormack S, Espana RA, Crocker A, Scammell TE (2006) Afferents to the orexin neurons of the rat brain. J Comp Neurol 494:845–861. doi:10.1002/cne.20859 PubMedGoogle Scholar
  211. Zhou Y, Bendor J, Hofmann L, Randesi M, Ho A, Kreek MJ (2006) Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal. J Endocrinol 191:137–145. doi:10.1677/joe.1.06960 PubMedGoogle Scholar
  212. Zislis G, Desai TV, Prado M, Shah HP, Bruijnzeel AW (2007) Effects of the CRF receptor antagonist d-Phe CRF((12–41)) and the alpha2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats. Neuropharmacology 53:958–966PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA

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