Alcohol
Volume 43, Issue 7 , Pages 491-498 , November 2009

Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond

  • Roberto Ciccocioppo

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39-0737-403313; fax: +39-0737-630618.
  • ,
  • Donald R. Gehlert

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Andrey Ryabinin

      Affiliations

    • Department of Behavioral Neuroscience, Oregon Health and Sciences University, Portland, OR 97239, USA
  • ,
  • Simranjit Kaur

      Affiliations

    • Department of Behavioral Neuroscience, Oregon Health and Sciences University, Portland, OR 97239, USA
  • ,
  • Andrea Cippitelli

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Annika Thorsell

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Anh D. Lê

      Affiliations

    • Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5S 2S1, Canada
  • ,
  • Philip A. Hipskind

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Chafiq Hamdouchi

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Jianliang Lu

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Erik J. Hembre

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Jeffrey Cramer

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Min Song

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • David McKinzie

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Michelle Morin

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Daina Economidou

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Serena Stopponi

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Nazzareno Cannella

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Simone Braconi

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Marsida Kallupi

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Giordano de Guglielmo

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • Maurizio Massi

      Affiliations

    • Department of Experimental Medicine and Public Health, University of Camerino, Via madonna delle Carceri, 62032 Camerino, Macerata, Italy
  • ,
  • David T. George

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Jody Gilman

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Jacqueline Hersh

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Johannes T. Tauscher

      Affiliations

    • Lilly Research Laboratories, Indianapolis, IN 46285, USA
  • ,
  • Stephen P. Hunt

      Affiliations

    • Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK
  • ,
  • Daniel Hommer

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
  • ,
  • Markus Heilig

      Affiliations

    • Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA

Received 30 March 2009 ,Accepted 12 August 2009.

References 

  1. Bachtell RK, Tsivkovskaia NO, Ryabinin AE. Strain differences in urocortin expression in the Edinger-Westphal nucleus and its relation to alcohol-induced hypothermia. Neuroscience. 2002;113:421–434
  2. Bachtell RK, Wang YM, Freeman P, Risinger FO, Ryabinin AE. Alcohol drinking produces brain region-selective changes in expression of inducible transcription factors. Brain Res. 1999;847:157–165
  3. Bachtell RK, Weitemier AZ, Galvan-Rosas A, Tsivkovskaia NO, Risinger FO, Phillips TJ, et al. The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption. J. Neurosci. 2003;23:2477–2487
  4. Bachtell RK, Weitemier AZ, Ryabinin AE. Lesions of the Edinger-Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption. Eur. J. Neurosci. 2004;20:1613–1623
  5. Bale TL, Vale WW. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu. Rev. Pharmacol. Toxicol. 2004;44:525–557
  6. Berglund MM, Hipskinnd PA, Gehlert DR. Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes. Exp. Biol. Med. (Maywood). 2003;228:217–244
  7. Bittencourt JC, Vaughan J, Arias C, Rissman RA, Vale WW, Sawchenko PE. Urocortin expression in rat brain: evidence against a pervasive relationship of urocortin-containing projections with targets bearing type 2 CRF receptors. J. Comp. Neurol. 1999;415:285–312
  8. Ciccocioppo R, Economidou D, Fedeli A, Angeletti S, Weiss F, Heilig M, et al. 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
  9. 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
  10. Ciccocioppo R, Economidou D, Rimondini R, Sommer W, Massi M, Heilig M. Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system. Biol. Psychiatry. 2007;61:4–12
  11. Dave JR, Eskay RL. Demonstration of corticotropin-releasing factor binding sites on human and rat erythrocyte membranes and their modulation by chronic ethanol treatment in rats. Biochem. Biophys. Res. Commun. 1986;136:137–144
  12. Economidou D, Fedeli A, Fardon RM, 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
  13. Economidou D, Hansson AC, Weiss F, Terasmaa A, Sommer WH, Cippitelli A, et al. Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat. Biol. Psychiatry. 2008;64:211–218
  14. 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
  15. Furmark T, Appel L, Michelgård A, Wahlstedt K, Ahs F, Zancan S, et al. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo. Biol. Psychiatry. 2005;58:132–142
  16. Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hipskind PA, Hamdouchi C, 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
  17. George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, et al. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science. 2008;319:1536–1539
  18. Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol. Psychiatry. 2002;7:254–275
  19. Gratzer D, Levitan RD, Sheldon T, Toneatto T, Rector NA, Goering P. Lifetime rates of alcoholism in adults with anxiety, depression, or co-morbid depression/anxiety: a community survey of Ontario. J. Affect. Disord. 2004;79:209–215
  20. Hawley RJ, Nemeroff CB, Bissette G, Guidotti A, Rawlings R, Linnoila M. Neurochemical correlates of sympathetic activation during severe alcohol withdrawal. Alcohol. Clin. Exp. Res. 1994;18:1312–1316
  21. Heilig M. Antisense inhibition of neuropeptide Y (NPY)-Y1 receptor expression blocks the anxiolytic-like action of NPY in amygdala and paradoxically increases feeding. Regul. Pept. 1995;59:201–205
  22. Higley JD, Hasert MF, Suomi SJ, Linnoila M. Nonhuman primate model of alcohol abuse: effect of early experience, personality, and stress on alcohol consumption. Proc. Natl. Acad. Sci. USA. 1991;88:7261–7265
  23. Hettema JM, Prescott CA, Kendler KS. The effects of anxiety, substance use and conduct disorders on risk of major depressive disorder. Psychol. Med. 2003;33:1423–1432
  24. Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol. Sci. 2003;24:580–588
  25. Inder WJ, Joyce PR, Ellis MJ, Evans MJ, Livesey JH, Donald RA. The effects of alcoholism on the hypothalamic-pituitary-adrenal axis: interaction with endogenous opioid peptides. Clin. Endocrinol. (Oxf). 1995;43:283–290
  26. Johnson RE, McCagh JC. Buprenorphine and naloxone for heroin dependence. Curr. Psychiatry Rep. 2000;2:519–526
  27. Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet. 2003;361:662–668
  28. Karlsson RM, Choe JS, Cameron HA, Thorsell A, Crawley JN, Holmes A, et al. The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice. Psychopharmacology (Berl.). 2008;195:547–557
  29. Koob GF. Stress, corticotropin-releasing factor, and drug addiction. Ann. N.Y. Acad. Sci. 1999;897:27–45
  30. Kozicz T, Yanaihara H, Arimura A. Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. J. Comp. Neurol. 1998;391:1–10
  31. 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
  32. Lê 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
  33. Liu X, Weiss F. Additive effects of drug cues on reinstatement of ethanol-seeking: exacerbation by history of dependence and role of concurent activation of CRF and opioid mechanisms. J. Neurosci. 2002;22:7856–7861
  34. Lovinger DM, Crabbe JC. Laboratory models of alcoholism: treatment target identification and insight into mechanisms. Nat. Neurosci. 2005;8:1471–1480
  35. 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
  36. May PJ, Reiner AJ, Ryabinin AE. Comparison of the distributions of urocortin-containing and cholinergic neurons in the perioculomotor midbrain of the cat and macaque. J. Comp. Neurol. 2008;507:1300–1316
  37. McLellan AT, Kushner H, Metzger D, Peters R, Smith I, Grissom G, et al. The Fifth Edition of the Addiction Severity Index. J. Subst. Abuse Treat. 1992;9:199–213
  38. Mollenauer S, Bryson R, Robison M, Sardo J, Coleman C. EtOH self-administration in anticipation of noise stress in C57BL/6J mice. Pharmacol. Biochem. Behav. 1993;46:35–38
  39. Monti PM, Rohsenow DJ, Rubonis AV, Niaura RS, Sirota AD, Colby SM, et al. Alcohol cue reactivity: effects of detoxification and extended exposure. J. Stud. Alcohol. 1993;54:235–245
  40. Montoya ID, Gorelick DA, Preston KL, Schroeder JR, Umbricht A, Cheskin LJ, et al. Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence. Clin. Pharmacol. Ther. 2004;75:34–48
  41. Nemeroff CB, Vale WW. The neurobiology of depression: inroads to treatment and new drug discovery. J. Clin. Psychiatry. 2005;66(Suppl 7):5–13
  42. O'Brien CP. A range of research-based pharmacotherapies for addiction. Science. 1997;278:66–70
  43. Picard PR, Tramer MR, McQuay HJ, Moore RA. Analgesic efficacy of peripheral opioids (all except intra-articular): a qualitative systematic review of randomised controlled trials. Pain. 1997;72:309–318
  44. Redrobe JP, Dumont Y, Herzog H, Quirion R. Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from Y2 receptor knockout mice. Behav. Brain Res. 2003;141:251–255
  45. 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
  46. Rivier C, Bruhn T, Vale W. Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF). J. Pharmacol. Exp. Ther. 1984;229:127–131
  47. Ryabinin AE, Bachtell RK, Freeman P, Risinger FO. ITF expression in mouse brain during acquisition of alcohol self-administration. Brain Res. 2001;890:192–195
  48. Ryabinin AE, Galvan-Rosas A, Bachtell RK, Risinger FO. High alcohol/sucrose consumption during dark circadian phase in C57BL/6J mice: involvement of hippocampus, lateral septum and urocortin-positive cells of the Edinger-Westphal nucleus. Psychopharmacology (Berl). 2003;165:296–305
  49. Ryabinin AE, Tsivkovskaia NO, Ryabinin SA. Urocortin 1-containing neurons in the human Edinger-Westphal nucleus. Neuroscience. 2005;134:1317–1323
  50. Ryabinin AE, Weitemier AZ. The urocortin 1 neurocircuit: ethanol-sensitivity and potential involvement in alcohol consumption. Brain Res. Rev. 2006;52:368–380
  51. Ryabinin AE, Yoneyama N, Tanchuck MA, Mark GP, Finn DA. Urocortin 1 microinjection into the mouse lateral septum regulates the acquisition and expression of alcohol consumption. Neuroscience. 2008;151:780–790
  52. Sajdyk TJ, Vandergriff MG, Gehlert DR. Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. Eur. J. Pharmacol. 1999;368:143–147
  53. Sigvardsson S, Bohman M, Cloninger CR. Replication of the Stockholm Adoption Study of alcoholism. Confirmatory cross-fostering analysis. Arch. Gen. Psychiatry. 1996;53:681–687
  54. Sharpe AL, Tsivkovskaia NO, Ryabinin AE. Ataxia and c-Fos expression in mice drinking ethanol in a limited access session. Alcohol. Clin. Exp. Res. 2005;29:1419–1426
  55. Sinha R, Krishnan-Sarin S, Farren C, O'Malley S. Naturalistic follow-up of drinking behavior following participation in an alcohol administration study. J. Subst. Abuse Treat. 1999;17:159–162
  56. Tatemoto K, Carlquist M, Mutt V. Neuropeptide Y–a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982;296:659–660
  57. Thiele TE, Marsh DJ, Ste ML, Bernstein IL, Palmiter RD. Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature. 1998;396:366–369
  58. Thorsell A, Svensson P, Wiklund L, Sommer W, Ekman R, Heilig M. Suppressed neuropeptide Y (NPY) mRNA in rat amygdala following restraint stress. Regul. Pept. 1998;75–76:247–254
  59. Thorsell A, Carlsson K, Ekman R, Heilig M. Behavioral and endocrine adaptation, and up-regulation of NPY expression in rat amygdala following repeated restraint stress. Neuroreport. 1999;10:3003–3007
  60. Thorsell A, Michalkiewicz M, Dumont Y, Quirion R, Caberlotto L, Rimondini R, et al. Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression. Proc. Natl. Acad. Sci. USA. 2000;97:12852–12857
  61. 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
  62. Thorsell A, Repunte-Canonigo V, O'Dell LE, Chen SA, King AR, Lekic D, et al. Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats. Brain. 2007;130:1330–1337
  63. Tschenett A, Singewald N, Carli M, Balducci C, Salchner P, Vezzani A, et al. Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. Eur. J. Neurosci. 2003;18:143–148
  64. Turek VF, Tsivkovskaia NO, Hyytia P, Harding S, Le AD, Ryabinin AE. Urocortin 1 expression in five pairs of rat lines selectively bred for differences in alcohol drinking. Psychopharmacology (Berl.). 2005;181:511–517
  65. Uhart M, Oswald L, McCaul ME, Chong R, Wand GS. Hormonal responses to psychological stress and family history of alcoholism. Neuropsychopharmacology. 2006;31:2255–2263
  66. Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, et al. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature. 1995;378:287–292
  67. Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence. Arch. Gen. Psychiatry. 1992;49:876–880
  68. Wahlestedt C, Yanaihara N, Hakanson R. Evidence for different pre- and post-junctional receptors for neuropeptide Y and related peptides. Regul. Pept. 1986;13:307–318
  69. Wand GS, Dobs AS. Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J. Clin. Endocrinol. Metab. 1991;72:1290–1295
  70. Weitemier AZ, Ryabinin AE. Brain region-specific regulation of urocortin 1 innervation and corticotropin-releasing factor receptor type 2 binding by ethanol exposure. Alcohol. Clin. Exp. Res. 2005;29:1610–1620
  71. Weitemier AZ, Tsivkovskaia NO, Ryabinin AE. Urocortin 1 distribution in mouse brain is strain-dependent. Neuroscience. 2005;132:729–740
  72. Weitemier AZ, Woerner A, Backstrom P, Hyytia P, Ryabinin AE. Expression of c-Fos in Alko alcohol rats responding for ethanol in an operant paradigm. Alcohol. Clin. Exp. Res. 2001;25:704–710
  73. Wilkins JN, Gorelick DA. Clinical neuroendocrinology and neuropharmacology of alcohol withdrawal. Recent Dev. Alcohol. 1986;4:241–263

PII: S0741-8329(09)00104-9

doi: 10.1016/j.alcohol.2009.08.003

Alcohol
Volume 43, Issue 7 , Pages 491-498 , November 2009