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Opiate Receptors and Antagonists pp 45–65Cite as

Imaging Human Brain Opioid Receptors: Applications to Substance Use Disorders

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Three types of opioid receptors (ORs: mu [μ], kappa [k], and delta [δ]) are differentially distributed throughout the brain. Historically, the |μOR has been of great est clinical interest because it mediates therapeutic effects (e.g., analgesia and cough suppression) and nontherapeutic effects (e.g., abuse and physical dependence) of opioid agonists. This “dual-edged sword” underlies the classical dilemma of balanc ing safety and efficacy when |μOR agonists are administered systemically to human subjects. Preclinical studies suggest that kOR- and δOR-specific agonists and antago nists could be useful in treating human substance use disorders, but the lack of such Food and Drug Administration (FDA)-approved medications significantly limits our understanding of the role of these molecular targets in the clinical setting. However, the μμOR-specific radiotracer [11C]-carfentanil has been used with positron emission tomography (PET) to elucidate the function of this endogenous system as it relates to substance use disorders, both with antagonists (e.g., naltrexone) and agonists (e.g., buprenorphine). The δOR-specific tracer [11C]-methyl-naltrindole is also available for human use, but has not yet been applied to substance use disorders, and a kOR-specific tracer has shown promise in preclinical testing. Advances in neuroscience and medication development are likely to yield significant progress that will improve our understanding of these disorders and clinical outcomes in the near future.

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References

  1. Bencherif B, Fuchs PN, Sheth R, Dannals RF, Campbell JN, Frost JJ. Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET). Pain 2002;99:589–598.

    Article  CAS  PubMed  Google Scholar 

  2. Jones AK, Cunningham VJ, Ha-Kawa S, Fujiwara T, Luthra SK, Silva S, Derbyshire S, Jones T. Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. Br J Rheumatol 1994;33:909–916.

    Article  CAS  PubMed  Google Scholar 

  3. Jones AK, Watabe H, Cunningham VJ, Jones T. Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET. Eur J Pain 2004;8:479–485.

    Article  CAS  PubMed  Google Scholar 

  4. Willoch F, Schindler F, Wester HJ, Empl M, Straube A, Schwaiger M, Conrad B, Tolle TR. Central poststroke pain and reduced opioid receptor binding within pain processing circuit ries: a [11C]diprenorphine PET study. Pain 2004;108:213–220.

    Article  CAS  PubMed  Google Scholar 

  5. Zubieta JK, Smith YR, Bueller J, Xu Y, Kilbourn M, Meyer C, Koeppe R, Stohler C. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 2001;293:311–315.

    Article  CAS  PubMed  Google Scholar 

  6. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 2003;299:1240–1243.

    Article  CAS  PubMed  Google Scholar 

  7. Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, Nichols TE, Stohler CS. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 2005;25:7754–7762.

    Article  CAS  PubMed  Google Scholar 

  8. Mayberg HS, Ross CA, Dannals RF, Ravert HT, Wagner HN Jr, Frost JJ. Elevated mu opiate receptors measured by PET in patients with depression. J Cereb Blood Flow Metab 1991a;11:S821.

    Google Scholar 

  9. Frost JJ, Mayberg HS, Fisher RS, Douglass KH, Dannals RF, Links JM, Wilson AA, Ravert HT, Rosenbaum AE, Snyder SH, Wagner HN Jr. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988;23:231–237.

    Article  CAS  PubMed  Google Scholar 

  10. Mayberg HS, Sadzot B, Meltzer CC, Fisher RS, Lesser RP, Dannals RF, Lever JR, Wilson AA, Ravert HT, Wagner HN Jr, Brian RN, Cromwell CC, Frost JJ. Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomogra phy. Ann Neurol 1991b;30:3–11.

    Article  CAS  Google Scholar 

  11. Chaturvedi K, Christoffers KH, Singh K, Howells RD. Structure and regulation of opioid receptors. Biopolymers 2000;55:334–346.

    Article  CAS  PubMed  Google Scholar 

  12. Philip AE, Poupaert JH, McCurdy CR. Opioid receptor-like 1 (ORL1) molecular “road map” to understanding ligand interaction and selectivity. Curr Top Med Chem 2005;5:325–340.

    Article  CAS  PubMed  Google Scholar 

  13. Reinscheid RK. The orphanin FQ/nociceptin receptor as a novel drug target in psychiatric disorders. CNS Neurol Disord Drug Targets 2006;5:219–224.

    Article  CAS  PubMed  Google Scholar 

  14. Elmer GI, Pieper JO, Goldberg SR, George FR. Opioid operant self-administration, analgesia, stimulation and respiratory depression in mu-deficient mice. Psychopharmacology (Berl) 1995;117:23–31.

    Article  CAS  Google Scholar 

  15. Maldonado R, Negus S, Koob GF. Precipitation of morphine withdrawal syndrome in rats by administration of mu-, delta- and kappa-selective opioid antagonists. Neuropharmacology 1992;31:1231–1241.

    Article  CAS  PubMed  Google Scholar 

  16. Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, Befort K, Dierich A, Le Meur M, Dolle P, Tzavara E, Hanoune J, Roques BP, Kieffer BL. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 1996;383:819–823.

    Article  CAS  PubMed  Google Scholar 

  17. Negus SS, Henriksen SJ, Mattox A, Pasternak GW, Portoghese PS, Takemori AE, Weinger MB, Koob GF. Effect of antagonists specific for mu, delta and kappa opioid receptors on the rein forcing effects of heroin in rats. J Pharmacol Exp Ther 1993;265:1245–1252.

    CAS  PubMed  Google Scholar 

  18. Oswald LM, Wand GS. Opioids and alcoholism. Physiol Behav 2004;81:339–358.

    Article  CAS  PubMed  Google Scholar 

  19. Gianoulakis C. Alcohol-seeking behavior: the roles of the hypothalamic-pituitary-adrenal axis and the endogenous opioid system. Alcohol Health Res World 1998;22:202–210.

    CAS  PubMed  Google Scholar 

  20. Froehlich JC. The neurobiology of ethanol-opioid interactions in ethanol reinforcement. Alcohol Clin Exp Res 1996;20:181–186.

    Article  Google Scholar 

  21. Gianoulakis C. Characterization of the effects of acute ethanol administration on the release of beta-endorphin peptides by the rat hypothalamus. Eur J Pharm 1990;180:21–29.

    Article  CAS  Google Scholar 

  22. Bailey A, Gianotti R, Ho A, Kreek MJ. Persistent upregulation of mu-opioid, but not adeno-sine, receptors in brains of long-term withdrawn escalating dose “binge” cocaine-treated rats. Synapse 2005;57:160–166.

    Article  CAS  PubMed  Google Scholar 

  23. Tang XC, McFarland K, Cagle S, Kalivas PW. Cocaine-induced reinstatement requires endogenous stimulation of mu-opioid receptors in the ventral pallidum. J Neurosci 2005;25:4512–4520.

    Article  CAS  PubMed  Google Scholar 

  24. Unterwald EM, Kreek MJ, Cuntapay M. The frequency of cocaine administration impacts cocaine-induced receptor alterations. Brain Res 2001;900:103–109.

    Article  CAS  PubMed  Google Scholar 

  25. Unterwald EM, Rubenfeld JM, Kreek MJ. Repeated cocaine administration upregulates kappa and mu, but not delta, opioid receptors. Neuroreport 1994;5:1613–1616.

    Article  CAS  PubMed  Google Scholar 

  26. Hammer RP Jr. Cocaine alters opiate receptor binding in critical brain reward regions. Synapse 1989;3:55–60.

    Article  CAS  PubMed  Google Scholar 

  27. Galeote L, Kieffer BL, Maldonado R, Berrendero F. Mu-opioid receptors are involved in the tolerance to nicotine antinociception. J Neurochem 2006;97:416–423.

    Article  CAS  PubMed  Google Scholar 

  28. Walters CL, Cleck JN, Kuo YC, Blendy JA. Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron 2005;46:933–943.

    Article  CAS  PubMed  Google Scholar 

  29. Pomerleau OF. Endogenous opioids and smoking: a review of progress and problems. Psychoneuroendocrinology 1998;23:115–130.

    Article  CAS  PubMed  Google Scholar 

  30. Davenport KE, Houdi AA, Van Loon GR. Nicotine protects against mu-opioid receptor antagonism by beta-funaltrexamine: evidence for nicotine-induced release of endogenous opioids in brain. Neurosci Lett 1990;113:40–46.

    Article  CAS  PubMed  Google Scholar 

  31. Jones AK, Luthra SK, Maziere B, Pike VW, Loch C, Crouzel C, Syrota A, Jones T. Regional cerebral opioid receptor studies with [11C]-diprenorphine in normal volunteers. J Neurosci Methods 1988;23:121–129.

    Article  CAS  PubMed  Google Scholar 

  32. Dannals RF, Ravert HT, Frost JJ, Wilson AA, Burns HD, Wagner HN Jr. Radiosynthesis of an opiate receptor binding radiotracer: [11C]-carfentanil. Int J Appl Radiat Isot 1985;36:303–306.

    Article  CAS  PubMed  Google Scholar 

  33. Frost JJ, Wagner HNJ, Dannals RF, Ravert HT, Wilson AA, Burns HD, Wong DF, McPherson RW, Rosenbaum AE, Kuhar MJ, Snyder SH. Imaging opiate receptors in the human brain by posi tron emission tomography. J Comput Assist Tomogr 1985;9:231–236.

    Article  CAS  PubMed  Google Scholar 

  34. Titeler M, Lyon RA, Kuhar MJ, Frost JF, Dannals RF, Leonhardt S, Bullock A, Rydelek LT, Price DL, Struble RG. Mu opiate receptors are selectively labelled by [3H]-carfentanil in human and rat brain. Eur J Pharmacol 1989;167:221–228.

    Article  CAS  PubMed  Google Scholar 

  35. Greenwald MK, Johanson, CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA. Effects of buprenorphine maintenance dose on mu-opioid receptor binding potential, plasma concentra tion, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology 2003;28:2000–2009.

    CAS  PubMed  Google Scholar 

  36. Greenwald MK, Johanson C-E, Bueller J, Chang Y, Moody DE, Kilbourn MR, Koeppe RA, Zubieta JK. Buprenorphine duration of action: mu-opioid receptor availability, pharmacoki-netic and behavioral indices. Biol Psychiatry 2007;61:101–110.

    Article  CAS  PubMed  Google Scholar 

  37. Ingman K, Hagelberg N, Aalto S, Nagren K, Juhakoski A, Karhuvaara S, Kallio A, Oikonen V, Hietala J, Scheinin H. Prolonged central μ-opioid receptor occupancy after single and repeated nalmefene dosing. Neuropsychopharmacology 2005;30:2245–2253.

    Article  CAS  PubMed  Google Scholar 

  38. Kim S, Wagner HN Jr, Villemagne VL, Kao PF, Dannals RF, Ravert HT, Joh T, Dixon RB, Civelek AC. Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by a dual-detector system. J Nucl Med 1997;38:1726–1731.

    CAS  PubMed  Google Scholar 

  39. Zubieta JK, Dannals RF, Frost JJ. Gender and age influences on human brain mu-opioid receptor binding measured by PET. Am J Psychiatry 1996;156:842–848.

    Google Scholar 

  40. Zubieta JK, Gorelick DA, Stauffer R, Ravert HT, Dannals RF, Frost JJ. Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving. Nat Med 1996;2:1225–1229.

    Article  CAS  PubMed  Google Scholar 

  41. Gorelick DA, Kim YK, Bencherif B, Boyd SJ, Nelson R, Copersino M, Endres CJ, Dannals RF, Frost JJ. Imaging brain mu-opioid receptors in abstinent cocaine users: time course and rela tion to cocaine craving. Biol Psychiatry 2005;57:1573–1582.

    Article  CAS  PubMed  Google Scholar 

  42. Bencherif B, Wand GS, McCaul ME, Kim YK, Ilgin N, Dannals RF, Frost JJ. Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry 2004;55:255–262.

    Article  CAS  PubMed  Google Scholar 

  43. Heinz A, Reimold M, Wrase J, Hermann D, Croissant B, Mundle G. Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 2005;62:57–64.

    Article  PubMed  Google Scholar 

  44. Scott DJ, Domino EF, Heitzeg MM, Koeppe RA, Ni L, Guthrie S, Zubieta JK. Smoking modulation of μ-opioid and dopamine D2 receptor mediated neurotransmission in humans. Neuropsychopharmacology 2007;32:450–457.

    Article  CAS  PubMed  Google Scholar 

  45. Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, Frost JJ. Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J Nucl Med 2005;46:1349–1351.

    CAS  PubMed  Google Scholar 

  46. Burke TR, Rice KC, Pert CB. Probes for narcotic receptor mediated phenomena. II. Synthesis of 17-methyl and 17-cyclopropylmethyl-3,14-dihydroxy-4,5 alpha-epoxy-6-beta-fluoromor-phinans (foxy and cyclofoxy) as models of opioid ligands suitable for positron emission transaxial tomography. Heterocycles 1985;23:69–99.

    Google Scholar 

  47. Carson RE, Channing MA, Blasberg RG, Dunn BB, Cohen RM, Rice KC, Herscovitch P. Comparison of bolus and infusion methods for receptor quantitation: application to [18F] cyclofoxy and positron emission tomography. J Cereb Blood Flow Metab 1993;13:24–42.

    CAS  PubMed  Google Scholar 

  48. Channing MA, Eckelman WC, Bennett JM, Burke TR, Rice KC. Radiosynthesis of [18F] 3-acetylcyclofoxy: a high affinity opiate antagonist. Int J Appl Radiat Isot 1985;36:429–433.

    Article  CAS  PubMed  Google Scholar 

  49. Pert CB, Danks JA, Channing MA, Eckelman WC, Larson SM, Bennett JM, Burke TR Rice KC. 3-[18F]Acetylcyclofoxy: a useful probe for the visualization of opiate receptors in living ani mals. FASEB Lett 1984;177:281–286.

    Article  CAS  Google Scholar 

  50. Rothman RB, McLean SA. An examination of the opiate receptor subtypes labeled by [3H] cyclofoxy: an opiate antagonist suitable for positron emission tomography. Biol Psychiatry 1988;22:423–458.

    Google Scholar 

  51. Kling MA, Carson RE, Borg L, Zametkin A, Matochik JA, Schluger J, Herscovitch P, Rice KC, Ho A, Eckelman WC, Kreek MJ. Opioid receptor imaging with positron emission tomography and [18F]cyclofoxy in long-term, methadone-treated former heroin addicts. J Pharmacol Exp Ther 2000;295:1070–1076.

    CAS  PubMed  Google Scholar 

  52. Lewis JW, Husbands SM. The orvinols and related opioids — high affinity ligands with diverse efficacy profiles. Curr Pharm Des 2004;10:717–732.

    Article  CAS  PubMed  Google Scholar 

  53. Sadzot B, Price JC, Mayberg HS, Douglass KH, Dannals RF, Lever JR, Ravert HT, Wilson AA, Wagner HN Jr, Feldman MA. Quantification of human opioid receptor concentration and affinity using high and low specific activity [11C]-diprenorphine and positron emission tomography. J Cereb Blood Flow Metab 1991;11:204–219.

    CAS  PubMed  Google Scholar 

  54. Melichar JK, Hume SP, Williams TM, Daglish MR, Taylor LG, Ahmad R, Malizia AL, Brooks DJ, Myles JS, Lingford-Hughes A, Nutt DJ. Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies. J Pharmacol Exp Ther 2005;312:309–315.

    Article  CAS  PubMed  Google Scholar 

  55. Lever JR, Scheffel U, Kinter CM, Ravert HT, Dannals RF, Wagner HN Jr, Frost JJ. In vivo binding of N1′-[11C]methyl)naltrindole to δ opioid receptors in mouse brain. Eur J Pharmacol 1992;216:459–460.

    Article  CAS  PubMed  Google Scholar 

  56. Madar I, Lever JR, Kinter CM, Scheffel U, Ravert HT, Musachio JL, Mathews WB, Dannals RF, Frost JJ. Imaging of δ opioid receptors in human brain by N1′-([11C]methyl)naltrindole and PET. Synapse 1996;24:19–28.

    Article  CAS  PubMed  Google Scholar 

  57. Smith JS, Zubieta JK, Price JC, Flesher JE, Madar I, Lever JR, Kinter CM, Dannals RF, Frost JJ. Quantification of δ-opioid receptors in human brain with N1′-([11C]methyl) naltrin-dole and positron emission tomography. J Cereb Blood Flow Metab 1999;19:956–966.

    Article  CAS  PubMed  Google Scholar 

  58. Lee MD, Wagner HD, Tanada S, Frost JJ, Bice AN, Dannals RF. Duration of occupancy of opiate receptors by naltrexone. J Nucl Med 1988;29:1207–1211.

    CAS  PubMed  Google Scholar 

  59. Verebey K, Volavka J, Mule SJ, Resnick RB (1976). Naltrexone: disposition, metabolism, and effects after acute and chronic dosing. Clin Pharmacol Ther 1976;20:315–328.

    CAS  PubMed  Google Scholar 

  60. Kaplan JL, Marx JA. Effectiveness and safety of intravenous nalmefene for emergency department patients with suspected narcotic overdose: a pilot study. Ann Emerg Med 1993;22:187–190.

    Article  CAS  PubMed  Google Scholar 

  61. Kaplan JL, Marx JA, Calabro JJ, Gin-Shaw SL, Spiller JD, Spivey WL, Gaddis GM, Zhao N, Harchelroad FP Jr. Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. Ann Emerg Med 1999;34:42–50.

    Article  CAS  PubMed  Google Scholar 

  62. Wang DS, Sternbach G, Varon J. Nalmefene: a long-acting opioid antagonist. Clinical applica tions in emergency medicine. J Emerg Med 1998;16:471–475.

    Article  CAS  PubMed  Google Scholar 

  63. Melichar JK, Nutt DJ, Malizia AL. Naloxone displacement at opioid receptor sites measured in vivo in the human brain. Eur J Pharmacol 2003;459:217–219.

    Article  CAS  PubMed  Google Scholar 

  64. Kristensen K, Christensen CB, Christup LL. The mu1, mu2, delta and kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Life Sci 1995;56:PL45–PL60.

    Article  CAS  PubMed  Google Scholar 

  65. Borgland SL, Connor M, Osborne PB, Furness JB, Christie MJ. Opioid agonists have different efficacy profiles for G protein activation, rapid desensitization, and endocytosis of mu-opioid receptors. J Biol Chem 2003;278:18776–18784.

    Article  CAS  PubMed  Google Scholar 

  66. Blake AD, Bot G, Freeman JC, Reisine T. Differential opioid agonist regulation of the mouse μ opioid receptor. J Biol Chem 1997;272:782–790.

    Article  CAS  PubMed  Google Scholar 

  67. Celver J, Xu M, Jin W, Lowe J, Chavkin C. Distinct domains of the mu-opioid receptor con trol uncoupling and internalization. Mol Pharmacol 2004;65:492–495.

    Article  Google Scholar 

  68. Haberstock-Debic H, Wein M, Barrot M, Colago EE, Rahman Z, Neve RL, Pickel VM, Nestler EJ, von Zastrow M, Svingos AL. Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons. J Neurosci 2003;23:4324–4332.

    CAS  PubMed  Google Scholar 

  69. Keith DE, Anton B, Murray SR, Zaki PA, Chu PC, Lissin DV, Monteillet-Agius G, Stewart PL, Evans CJ, von Zastrow M. Mu-opioid receptor internalization: opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain. Mol Pharmacol 1998;53:377–384.

    CAS  PubMed  Google Scholar 

  70. Shapira M, Keren O, Gafni M, Sarne Y. Diverse pathways mediate delta-opioid receptor down regulation within the same cell. Mol Brain Res 2001;96:142–150.

    Article  CAS  PubMed  Google Scholar 

  71. Snyder SH, Childers SR. Opiate receptors and opioid peptides. Ann Rev Neurosci 1979;2:35–64.

    Article  CAS  PubMed  Google Scholar 

  72. Richards ML, Sadee W. In vivo opiate receptor binding of oripavines to mu, delta and kappa sites in rat brain as determined by an ex vivo labeling method. Eur J Pharmacol 1985;114:343–353.

    Article  CAS  PubMed  Google Scholar 

  73. Negus SS, Bidlack JM, Mello NK, Furness MS, Rice KC, Brandt MR. Delta opioid antagonist effects of buprenorphine in rhesus monkeys. Behav Pharmacol 2002;13:557–570.

    CAS  PubMed  Google Scholar 

  74. Huang P, Kehner GB, Cowan A, Liu-Chen L-Y. Comparison of pharmacological activities of buprenorphine and nor-buprenorphine: nor-buprenorphine is a potent opioid agonist. J Pharmacol Exp Ther 2001;297:688–695.

    CAS  PubMed  Google Scholar 

  75. Wnendt S, Kruger T, Janocha E, Hildebrandt D, Englberger W. Agonist effect of buprenorphine in a nociceptin/OFQ receptor-triggered report gene assay. Mol Pharmacol 1999;56:334–338.

    CAS  PubMed  Google Scholar 

  76. Hawkinson JE, Acosta-Burruel M, Espitia SA. Opioid activity profiles indicate simi larities between the nociceptin/orphanin FQ and opioid receptors. Eur J Pharmacol 2000;389:107–114.

    Article  CAS  PubMed  Google Scholar 

  77. Yamamoto T, Shono K, Tanabe S. Buprenorphine activates mu- and opioid receptor like-1 receptors simultaneously, but the analgesic effect is mainly mediated by mu receptor activa tion in the rat formalin test. J Pharmacol Exp Ther 2006;318:206–213.

    Article  CAS  PubMed  Google Scholar 

  78. Zubieta JK, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, Koeppe RA, Schuster CR, Johanson, CE. Buprenorphine-induced changes in mu-opioid receptor avail ability in male heroin-dependent volunteers: a preliminary study. Neuropsychopharmacology 2000;23:326–334.

    Article  CAS  PubMed  Google Scholar 

  79. Greenwald MK. Human experimental therapeutic models in opioid dependence: translational research advances and implications. In: McKenna CR (Ed.), Trends in Substance Abuse Research, 2007;1–55. New York: Nova Science Publishers, Inc.

    Google Scholar 

  80. Sobel B-F, Sigmon SC, Walsh SL, Johnson RE, Liebson IA, Nuwayser ES, Kerrigan JH, Bigelow GE. Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification. Drug Alcohol Depend 2004;73:11–22.

    Article  CAS  PubMed  Google Scholar 

  81. Sigmon SC, Wong CJ, Chausmer AL, Liebson IA, Bigelow GE. Evaluation of an injection depot formulation of buprenorphine: placebo comparison. Addiction 2004;99:1439–1449.

    Article  PubMed  Google Scholar 

  82. Comer SD, Collins ED, Kleber HD, Nuwayser ES, Kerrigan JH, Fischman MW. Depot naltrexone: long-lasting antagonism of the effects of heroin in humans. Psychopharmacology (Berl) 2002;159:351–360.

    Article  CAS  Google Scholar 

  83. Campbell BK, Wander N, Stark MJ, Holbert T. Treating cigarette smoking in drug-abusing clients. J Subst Abuse Treat 1995;12:89–94.

    Article  CAS  PubMed  Google Scholar 

  84. Frosch DL, Shoptaw S, Jarvik ME, Rawson RA, Ling W. Interest in smoking cessation among methadone maintained outpatients. J Addict Dis 1998;17:9–19.

    Article  CAS  PubMed  Google Scholar 

  85. Navaratnam V, Foong K. Adjunctive drug use among opiate addicts. Curr Med Res Opin 1990;11:611–619.

    CAS  PubMed  Google Scholar 

  86. Stark MJ, Campbell BK. Drug use and cigarette smoking in applicants for drug abuse treat ment. J. Subst Abuse 1993;5:175–181.

    Article  CAS  PubMed  Google Scholar 

  87. Steinmiller CL, Greenwald MK. Factors associated with non-medical use of prescription opioids among heroin abusing research volunteers. Exp Clin Psychopharmacol 2007;15:492–500.

    Article  PubMed  Google Scholar 

  88. Houdi AA, Dasgupta R, Kindy MS. Effect of nicotine use and withdrawal on brain pre-proenkephalin A mRNA. Brain Res 1998;799:257–263.

    Article  CAS  PubMed  Google Scholar 

  89. Malin DH, Lake JR, Payne MC, Short PE, Carter VA, Cunningham JS, Wilson OB. Nicotine alleviation of nicotine abstinence syndrome is naloxone-reversible. Pharmacol Biochem Behav 1996;53:81–85.

    Article  CAS  PubMed  Google Scholar 

  90. Rasmussen DD. Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelano-cortin gene expression and neuroendocrine regulation. Psychoneuroendocrin-ology 1998;23:245–259.

    Article  CAS  Google Scholar 

  91. Wewers ME, Dhatt RK, Snively TA, Tejwani GA. The effect of chronic administration of nicotine on antinociception, opioid receptor binding and met-enkephalin levels in rats. Brain Res 1999;822:107–113.

    Article  CAS  PubMed  Google Scholar 

  92. Krishnan-Sarin S, Rosen MI, O'Malley SS. Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence. Arch Gen Psychiatry 1999;56:663–668.

    CAS  Google Scholar 

  93. Marco AP, Greenwald MK, Higgins MS. A preliminary study of 24-hour post-Cesarean patient-controlled analgesia: postoperative pain reports and morphine requests/utilization are greater in abstaining smokers than non-smokers. Med Sci Monit 2005;11:255–261.

    Google Scholar 

  94. Gorelick DA, Rose J, Jarvik ME. Effect of naloxone on cigarette smoking. J Subst Abuse 1988;1:153–159.

    Article  PubMed  Google Scholar 

  95. Karras A, Kane JM. Naloxone reduces cigarette smoking. Life Sci 1980;27:1541–1545.

    Article  CAS  PubMed  Google Scholar 

  96. Nemeth-Coslett R, Heningfield JE, O'Keeffe MK, Griffiths RR. Effects of mecamylamine on human cigarette smoking and subjective ratings. Psychopharmacology 1986;88:420–425.

    Article  CAS  PubMed  Google Scholar 

  97. Sutherland G, Stapleton JA, Russell MAH. Naltrexone, smoking behaviour and cigarette withdrawal. Psychopharmacology 1995;120:418–425.

    Article  CAS  PubMed  Google Scholar 

  98. Reid LD, Delconte JD, Nichols ML, Bilsky EJ, Hubbell CL. Tests of opioid deficiency hypotheses of alcoholism. Alcohol 1991;8:247–257.

    Article  CAS  PubMed  Google Scholar 

  99. Gianoulakis C, Chan JS, Kalant H, Chretien M. Chronic ethanol treatment alters the biosynthesis of beta-endorphin by the rat neurointermediate lobe. Can J Physiol Pharmacol 1983;61:967–976.

    CAS  PubMed  Google Scholar 

  100. Schulz R, Wuster M, Duka T, Herz A. Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. Psychopharmacology 1980;68:221–227.

    Article  CAS  PubMed  Google Scholar 

  101. Froehlich JC, Harts J, Lumeng L, Li TK. Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. Pharmacol Biochem Behav 1990;35:385–390.

    Article  CAS  PubMed  Google Scholar 

  102. Hubbell CL, Czirr SA, Hunter GA, Beaman CM, LeCann NC, Reid LD. Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations. Alcohol 1986;3:39–53.

    Article  CAS  PubMed  Google Scholar 

  103. Marfaing-Jallat P, Miceli D, LeMagnen J. Decrease in ethanol consumption by naloxone in naïve and dependent rats. Pharmacol Biochem Behav 1983;18:S537–S539.

    Article  Google Scholar 

  104. Samson HH, Doyle TF. Oral ethanol self-administration in the rat: effect of naloxone. Pharmacol Biochem Behav 1985;22:91–99.

    Article  CAS  PubMed  Google Scholar 

  105. Weiss F, Mitchiner M, Bloom FE, Koob GF. Free-choice responding for ethanol versus water in alcohol preferring (P) and unselected Wistar rats is differentially modified by naloxone, bromocriptine, and methysergide. Psychopharmacology 1990;101:178–186.

    Article  CAS  PubMed  Google Scholar 

  106. Altshuler HL, Phillips PE, Feinhandler DA. Alteration of ethanol self-administration by naltrexone. Life Sci 1980;26:679

    Article  CAS  PubMed  Google Scholar 

  107. Kornet M, Goosen C, Van Ree JM. Effect of naltrexone on alcohol consumption during chronic alcohol drinking and after a period of imposed abstinence in free-choice drinking rhesus monkeys. Psychopharmacology 1991;104:367–376.

    Article  CAS  PubMed  Google Scholar 

  108. Myers RD, Borg S, Mossberg R. Antagonism by naltrexone of voluntary alcohol selection in the chronically drinking macaque monkey. Alcohol 1986;3:383–388.

    Article  CAS  PubMed  Google Scholar 

  109. Volpicelli JR, Davis MA, Olgin JE. Naltrexone blocks the post-shock increase of ethanol consumption. Life Sci 1986;38:841–847.

    Article  CAS  PubMed  Google Scholar 

  110. Hyytia P, Kiianmaa K. Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats. Alcohol Clin Exp Res 2001;25:25–33.

    Article  CAS  PubMed  Google Scholar 

  111. Krishnan-Sarin S, Jing SL, Kurtz DL, Zweifel M, Portoghese PS, Li T-K, Froehlich JC. The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference. Psychopharmacology 1995a;120:177–185.

    Article  CAS  Google Scholar 

  112. Krishnan-Sarin S, Portoghese PS, Li T-K, Froehlich JC. The delta opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference. Pharmacol Biochem Behav 1995b;52:153–159.

    Article  CAS  Google Scholar 

  113. Krishnan-Sarin S, Wand GS, Li XW, Portoghese PS, Froehlich JC. Effect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking. Pharmacol Biochem Behav 1998;59:627–635.

    Article  CAS  PubMed  Google Scholar 

  114. Stromberg MF, Casale M, Volpicelli L, Volpicelli JR, O'Brien CP. A comparison of the effects of the opioid antagonists naltrexone, naltrindole, and beta-funaltrexamine on ethanol consumption in the rat. Alcohol 1998;15:281–289

    Article  CAS  PubMed  Google Scholar 

  115. O'Malley SS. Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse. Alcohol 1996;1:77–81.

    Google Scholar 

  116. O'Brien CP, Volpicelli LA, Volpicelli JR. Naltrexone in the treatment of alcoholism: a clinical review. Alcohol 1996;13:35–39.

    Article  PubMed  Google Scholar 

  117. Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA. Naltrexone in the treatment of alcohol dependence. N Engl J Med 2001;345:1734–1739.

    Article  CAS  PubMed  Google Scholar 

  118. Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelertner J, Volpicelli JR, O'Brien CP. A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 2003;28:1546–1552.

    Article  CAS  PubMed  Google Scholar 

  119. Drobes DJ, Anton RF, Thomas SE, Voronin K. A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene. Neuropsychopharmacology 2003;28:755–764.

    Article  CAS  PubMed  Google Scholar 

  120. O'Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek MJ. Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothala-mo-pituitary-adrenocortical axis. Psychopharmacology 2002;160:19–29.

    Article  PubMed  CAS  Google Scholar 

  121. Clow DW, Hammer RP Jr, Kirstein CL, Spear LP. Gestational cocaine exposure increases opiate receptor binding in weanling offspring. Brain Res Dev Brain Res 1991;59:179–185.

    Article  CAS  PubMed  Google Scholar 

  122. Cowen MS, Lawrence AJ. The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuropsychopharmacol Biol Psychiatry 1999;23:1171–1212.

    Article  CAS  PubMed  Google Scholar 

  123. Mello NK, Negus SS. Interactions between kappa opioid agonists and cocaine. Preclinical studies. Ann NY Acad Sci 2000;909:104–132.

    CAS  Google Scholar 

  124. Sheffler DJ, Roth BL. Salvinorin A: the “magic mint” hallucinogen finds a molecular target in the kappa opioid receptor. Trends Pharmacol Sci 2003;24:107–109.

    Article  CAS  PubMed  Google Scholar 

  125. Mazarati A, Liu H, Wasterlain C. Opioid peptide pharmacology and immunocytochemistry in an animal model of self-sustaining status epilepticus. Neuroscience 1999;89:167–173.

    Article  CAS  PubMed  Google Scholar 

  126. Solbrig V, Adrian R, Baratta J, Lauterborn JC, Koob GF. Kappa opioid control of seizures produced by a virus in an animal model. Brain 2006;129:642–654.

    Article  PubMed  Google Scholar 

  127. Talbot PS, Narendran R, Butelman ER, Huang Y, Ngo K, Slifstein M, Martinez D, Laruelle M, Hwang DR. 11C-GR103545, a radiotracer for imaging kappa-opioid receptors in vivo with PET: synthesis and evaluation in baboons. J Nucl Med 2005;46:484–494.

    CAS  PubMed  Google Scholar 

  128. Spanagel R, Herz A, Shippenberg TS. Opposing tonically active endogenous opioid sys tems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci USA 1992; 89:2046–2050.

    Article  CAS  PubMed  Google Scholar 

  129. Trujillo KA, Akil H. Changes in prodynorphin peptide content following treatment with morphine or amphetamine: possible role in mechanisms of action of drugs of abuse. NIDA Res Monogr 1989;95:550–551.

    CAS  PubMed  Google Scholar 

  130. DiChiara G, Imperato A. Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 1988;244:1067–1080.

    CAS  Google Scholar 

  131. Devine DP, Leone P, Pocock D, Wise RA. Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies. J Pharmacol Exp Ther 1993;266:1236–1246.

    CAS  PubMed  Google Scholar 

  132. Maisonneuve IM, Archer S, Glick SD. U50,488 a K opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens of rats. Neurosci Lett 1994;181:57–60.

    Article  CAS  PubMed  Google Scholar 

  133. Glick SD, Maisonneuve IM, Raucci J, Archer S. Kappa opioid inhibition of morphine and cocaine self-administration in rats. Brain Res 1995;681:147–152.

    Article  CAS  PubMed  Google Scholar 

  134. Walsh SL, Geter-Douglas B, Strain EC, Bigelow GE. Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans. J Pharmacol Exp Ther 2001;299:147–158.

    CAS  PubMed  Google Scholar 

  135. Preston KL, Umbricht A, Schroeder JR, Abreu ME, Epstein DH, Pickworth WB. Cyclazocine: comparison to hydromorphone and interaction with cocaine. Behav Pharmacol 2004;15:91–102.

    Article  CAS  PubMed  Google Scholar 

  136. Martin WR, Gorodetzky CW, McClane TK. An experimental study in the treatment of nar cotic addicts with cyclazocine. Clin Pharmacol Ther 1966;7:455–464.

    CAS  PubMed  Google Scholar 

  137. Reece PA, Sedman AJ, Rose DS, Wright R, Dawkins R, Rajagopalan R. Diuretic effects, pharmacokinetics, and safety of a new centrally acting kappa-opioid agonist (CI-977) in humans. J Clin Pharmacol 1994;34:1126–1132.

    CAS  PubMed  Google Scholar 

  138. Ananthan S. Opioid ligands with mixed mu/delta opioid receptor interactions: an emerging approach to novel analgesics. AAPS J 2006;8:E118–E125.

    Article  CAS  PubMed  Google Scholar 

  139. Gallantine EL, Meert TF. A comparison of the antinociceptive and adverse effects of the mu-opioid agonist morphine and the delta-opioid agonist SNC80. Basic Clin Pharmacol Toxicol 2005;97:39–51.

    Article  CAS  PubMed  Google Scholar 

  140. Su YF, McNutt RW, Chang KJ. Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception. J Pharmacol Exp Ther 1998;287:815–823.

    CAS  PubMed  Google Scholar 

  141. Negus SS, Gatch MB, Mello NK, Zhang X, Rice KC. Behavioral effects of the delta-selective opioid agonist SNC80 and related compounds in rhesus monkeys. J Pharmacol Exp Ther 1998;286:362–375.

    CAS  PubMed  Google Scholar 

  142. Broom DC, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH. Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats. Neuropsychopharmacology 2002;26:744–755.

    Article  CAS  PubMed  Google Scholar 

  143. Tejedor-Real P, Mico JA, Smadja C, Maldonado R, Roques BP, Gilbert-Rahola J. Involvement of delta-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model. Eur J Pharmacol 1998;31:1–7.

    Article  Google Scholar 

  144. Torregrossa MM, Folk JE, Rice KC, Watson SJ, Woods JH. Chronic administration of the delta opioid receptor agonist (+6 and antidepressants on behavior in the forced swim test and BDNF mRNA expression in rats. Psychopharmacology (Berl) 2005;183:31–40.

    Article  CAS  Google Scholar 

  145. Perrine SA, Hoshaw BA, Unterwald EM. Delta opioid receptor ligands modulate anxiety-like behaviors in the rat. Br J Pharmacol 2006;147:864–872.

    Article  CAS  PubMed  Google Scholar 

  146. Saitoh A, Kimura Y, Suzuki T, Kawai K, Nagase H, Kamei J. Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioral mod els in rodents. J Pharmacol Sci 2004;95:374–380.

    Article  CAS  PubMed  Google Scholar 

  147. Jutkiewicz EM, Baladi MG, Folk JE, Rice KC, Woods JH. The convulsive and electroen-cephalographic changes produced by nonpeptidic delta-opioid agonists in rats: comparison with pentylenetetrazol. J Pharmacol Exp Ther 2006;317:1337–1348.

    Article  CAS  PubMed  Google Scholar 

  148. Jutkiewicz EM, Rice KC, Traynor JR, Woods JH. Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats. Psychopharmacology (Berl) 2005;182:588–596.

    Article  CAS  Google Scholar 

  149. Schreckenberger M, Klega A, Grunder G, Buchholz HG, Scheurich A, Schirrmacher R, Schirrmacher E, Muller C, Henriksen G, Bartenstein P. Opioid receptor PET reveals the psychobiologic correlates of reward processing. J Nucl Med 2008;49:1257–1261.

    Article  PubMed  Google Scholar 

  150. Sprenger T, Valet M, Boecker H, Henriksen G, Spilker ME, Willoch F, Wagner KJ, Wester HJ, Tolle TR. Opioidergic activation in the medial pain system after heat pain. Pain 2006;122:63–67.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

NIH Grant P50 DA00254 and Joe Young, Sr. Funds from the State of Michigan supported the preparation of this chapter.

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  1. Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, 48207

    Mark K. Greenwald & Caren L. Steinmiller

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Correspondence to Mark K. Greenwald .

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  1. Life Sciences/Toxicology, Alkermes, Inc., Cambridge, MA, 02139, USA

    Reginald L. Dean III

  2. Department of Pharmacology, College of Osteopathic Medicine, University of New England, Biddleford, ME, 04005, USA

    Edward J. Bilsky

  3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    S. Stevens Negus

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Greenwald, M.K., Steinmiller, C.L. (2009). Imaging Human Brain Opioid Receptors: Applications to Substance Use Disorders. In: Dean, R.L., Bilsky, E.J., Negus, S.S. (eds) Opiate Receptors and Antagonists. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-197-0_3

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