Skip to main content
SpringerLink
Log in
Book cover

Drugs for Relapse Prevention of Alcoholism pp 49–58Cite as

Naltrexone: preclinical data

  • Chapter

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Blumberg H, Dayton HB (1973) Naloxone, naltrexone, and related noroxymorphones. Adv Biochem Psychopharmacol 8: 33–43

    PubMed  CAS  Google Scholar 

  2. Braude MC, Morrison JM (1976) Preclinical toxicity studies of naltrexone. NIDA Res Monogr 9: 16–26

    PubMed  Google Scholar 

  3. Blasig J, Hollt V, Herz A, Paschelke G (1976) Comparison of withdrawal precipitating properties of various morphine antagonists and partial agonists in relation to their stereospecific binding to brain homogenates. Psychopharmacologia 46: 41–51

    PubMed  CAS  Google Scholar 

  4. Valentino RJ, Katz JL, Medzihradsky F, Woods JH (1983) Receptor binding, antagonist, and withdrawal precipitating properties of opiate antagonists. Life Sci 32: 2887–2896

    Article  PubMed  CAS  Google Scholar 

  5. Millan MJ (1989) Kappa-opioid receptor-mediated antinociception in the rat. I. Comparative actions of mu-and kappa-opioids against noxious thermal, pressure and electrical stimuli. J Pharmacol Exp Ther 251: 334–341

    PubMed  CAS  Google Scholar 

  6. Gillan MG, Kosterlitz HW, Paterson SJ (1980) Comparison of the binding characteristics of tritiated opiates and opioid peptides. Br J Pharmacol 70: 481–490

    PubMed  CAS  Google Scholar 

  7. Magnan J, Paterson SJ, Tavani A, Kosterlitz HW (1982) The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn Schmiedebergs Arch Pharmacol 319: 197–205

    Article  PubMed  CAS  Google Scholar 

  8. O’Balley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 49: 881–887

    Google Scholar 

  9. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49: 876–880

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26: 679–688

    Article  PubMed  CAS  Google Scholar 

  13. Critcher EC, Lin CI, Patel J, Myers RD (1983) Attenuation of alcohol drinking in tetrahydroiso-quinoline-treated rats by morphine and naltrexone. Pharmacol Biochem Behav 18: 225–229

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Le AD, Sellers EM (1994) Interaction between opiate and 5-HT3 receptor antagonists in the regulation of alcohol intake. Alcohol Alcohol Suppl 2: 545–549

    PubMed  CAS  Google Scholar 

  17. Franck J, Lindholm S, Raaschou P (1998) Modulation of volitional ethanol intake in the rat by central delta-opioid receptors. Alcohol Clin Exp Res 22: 1185–1189

    PubMed  CAS  Google Scholar 

  18. Koistinen M, Tuomainen P, Hyytia P, Kiianmaa K (2001) Naltrexone suppresses ethanol intake in 6-hydroxydopamine-treated rats. Alcohol Clin Exp Res 25: 1605–1612

    PubMed  CAS  Google Scholar 

  19. Stromberg MF, Mackler SA, Volpicelli JR, O’Brien CP (2001) Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption. Alcohol 23: 109–116

    Article  PubMed  CAS  Google Scholar 

  20. Coonfield DL, Hill KG, Kaczmarek HJ, Ferraro FM, 3rd, Kiefer SW (2002) Low doses of naltrexone reduce palatability and consumption of ethanol in outbred rats. Alcohol 26: 43–47

    Article  PubMed  CAS  Google Scholar 

  21. Gonzales RA, Weiss F (1998) Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. J Neurosci 18: 10663–10671

    PubMed  CAS  Google Scholar 

  22. June HL, Grey C, Warren-Reese C, Durr LF, Ricks-Cord A, Johnson A, McCane S, Williams LS, Mason D, Cummings R et al. (1998) The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: preclinical studies in ethanol-preferring and outbred Wistar rats. Alcohol Clin Exp Res 22: 2174–2185

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Williams KL, Winger G, Pakarinen ED, Woods JH (1998) Naltrexone reduces ethanol-and sucrose-reinforced responding in rhesus monkeys. Psychopharmacology (Berl) 139: 53–61

    CAS  Google Scholar 

  25. Middaugh LD, Kelley BM, Cuison ER, Jr, Groseclose CH (1999) Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice. Alcohol Clin Exp Res 23: 456–464

    PubMed  CAS  Google Scholar 

  26. Rodefer JS, Campbell UC, Cosgrove KP, Carroll ME (1999) Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys. Psychopharmacology 141: 436–446

    Article  PubMed  CAS  Google Scholar 

  27. Williams KL, Woods JH (1999) Naltrexone reduces ethanol-and/or water-reinforced responding in rhesus monkeys: effect depends upon ethanol concentration. Alcohol Clin Exp Res 23: 1462–1467

    PubMed  CAS  Google Scholar 

  28. Carroll ME, Cosgrove KP, Campbell UC, Morgan AD, Mickelberg JL (2000) Reductions in ethanol, phencyclidine, and food-maintained behavior by naltrexone pretreatment in monkeys is enhanced by open economic conditions. Psychopharmacology 148: 412–422

    Article  PubMed  CAS  Google Scholar 

  29. Middaugh LD, Lee AM, Bandy AL (2000) Ethanol reinforcement in nondeprived mice: effects of abstinence and naltrexone. Alcohol Clin Exp Res 24: 1172–1179

    PubMed  CAS  Google Scholar 

  30. Shelton KL, Grant KA (2001) Effects of naltrexone and Ro 15-4513 on a multiple schedule of ethanol and Tang self-administration. Alcohol Clin Exp Res 25: 1576–1585

    PubMed  CAS  Google Scholar 

  31. Williams KL, Kane EC, Woods JH (2001) Interaction of morphine and naltrexone on oral ethanol self-administration in rhesus monkeys. Behav Pharmacol 12: 325–333

    PubMed  CAS  Google Scholar 

  32. Myers RD, Lankford MF (1996) Suppression of alcohol preference in high alcohol drinking rats: efficacy of amperozide versus naltrexone. Neuropsychopharmacology 14: 139–149

    Article  PubMed  CAS  Google Scholar 

  33. Holter SM, Spanagel R (1999) Effects of opiate antagonist treatment on the alcohol deprivation effect in long-term ethanol-experienced rats. Psychopharmacology 145: 360–369

    PubMed  CAS  Google Scholar 

  34. Goodwin FL, Campisi M, Babinska I, Amit Z (2001) Effects of naltrexone on the intake of ethanol and flavored solutions in rats. Alcohol 25: 9–19

    Article  PubMed  CAS  Google Scholar 

  35. McMillen BA, Williams HL (1995) Volitional consumption of ethanol by fawn-hooded rats: effects of alternative solutions and drug treatments. Alcohol 12: 345–350

    PubMed  CAS  Google Scholar 

  36. Davidson D, Amit Z (1997) Effect of ethanol drinking and naltrexone on subsequent drinking in rats. Alcohol 14: 581–584

    Article  PubMed  CAS  Google Scholar 

  37. Middaugh LD, Bandy AL (2000) Naltrexone effects on ethanol consumption and response to ethanol conditioned cues in C57BL/6 mice. Psychopharmacology 151: 321–327

    Article  PubMed  CAS  Google Scholar 

  38. Rezvani AH, Overstreet DH, Mason GA, Janowsky DS, Hamedi M, Clark E, Jr, Yang Y (2000) Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats. Alcohol Alcoholism 35: 76–83

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  40. Kornet M, Goosen C, Van Ree JM (1992) Opioid modulation of alcohol intake in monkeys by low doses of naltrexone and morphine. Ann N Y Acad Sci 654: 469–471

    PubMed  CAS  Google Scholar 

  41. Romberg R, Sarton E, Teppema L, Matthes HW, Kieffer BL, Dahan A (2003) Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and micro-opioid receptor deficient mice. Br J Anaesth 91: 862–870

    Article  PubMed  CAS  Google Scholar 

  42. Charness ME, Gordon AS, Diamond I (1983) Ethanol modulation of opiate receptors in cultured neural cells. Science 222: 1246–1248

    PubMed  CAS  Google Scholar 

  43. Tabakoff B, Hoffman PL (1983) Alcohol interactions with brain opiate receptors. Life Sci 32: 197–204

    Article  PubMed  CAS  Google Scholar 

  44. Olive MF, Koenig HN, Nannini MA, Hodge CW (2001) Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine. J Neurosci 21: RC184

    PubMed  CAS  Google Scholar 

  45. Marinelli PW, Quirion R, Gianoulakis C (2003) A microdialysis profile of beta-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Psychopharmacology (Berl) 169: 60–67

    CAS  Google Scholar 

  46. Williams KL, Woods JH (1998) Oral ethanol-reinforced responding in rhesus monkeys: effects of opioid antagonists selective for the mu-, kappa-, or delta-receptor. Alcohol Clin Exp Res 22: 1634–1639

    PubMed  CAS  Google Scholar 

  47. Nation JR, Horger BA, Pugh CK, Bratton GR, Rowe LD (1990) The effects of naltrexone on cadmium-induced increases in oral ethanol self-administration. Alcohol 7: 17–20

    Article  PubMed  CAS  Google Scholar 

  48. Iso H, Brush FR (1991) Opposite effects of naltrexone on ETOH intake by Syracuse high and low avoidance rats. Alcohol 8: 443–448

    Article  PubMed  CAS  Google Scholar 

  49. Phillips TJ, Wenger CD, Dorow JD (1997) Naltrexone effects on ethanol drinking acquisition and on established ethanol consumption in C57BL/6J mice. Alcohol Clin Exp Res 21: 691–702

    PubMed  CAS  Google Scholar 

  50. Cowen MS, Rezvani AH, Jarrott B, Lawrence AJ (1999) Ethanol consumption by Fawn-Hooded rats following abstinence: effect of naltrexone and changes in mu-opioid receptor density. Alcohol Clin Exp Res 23: 1008–1014

    PubMed  CAS  Google Scholar 

  51. Bienkowski P, Kostowski W, Koros E (1999) Ethanol-reinforced behaviour in the rat: effects of naltrexone. Eur J Pharmacol 374: 321–327

    PubMed  CAS  Google Scholar 

  52. Stromberg MF, Volpicelli JR, O’Brien CP (1998) Effects of naltrexone administered repeatedly across 30 or 60 days on ethanol consumption using a limited access procedure in the rat. Alcohol Clin Exp Res 22: 2186–2191

    PubMed  CAS  Google Scholar 

  53. Sinclair JD (1990) Drugs to decrease alcohol drinking. Ann Med 22: 357–362

    Article  PubMed  CAS  Google Scholar 

  54. Gardell LR, Reid LD, Boedeker KL, Liakos TM, Hubbell CL (1997) Isradipine and naltrexone in combination with isradipine interact with a period of abstinence to reduce rats’ intakes of an alcoholic beverage. Alcohol Clin Exp Res 21: 1592–1598

    PubMed  CAS  Google Scholar 

  55. Gardell LR, Whalen CA, Chattophadyay S, Cavallaro CA, Hubbell CL, Reid LD (1997) Combination of naltrexone and fluoxetine on rats’ propensity to take alcoholic beverage. Alcohol Clin Exp Res 21: 1435–1439

    PubMed  CAS  Google Scholar 

  56. Boyle AE, Stewart RB, Macenski MJ, Spiga R, Johnson BA, Meisch RA (1998) Effects of acute and chronic doses of naltrexone on ethanol self-administration in rhesus monkeys. Alcohol Clin Exp Res 22: 359–366

    PubMed  CAS  Google Scholar 

  57. Cramer CM, Gardell LR, Boedeker KL, Harris JR, Hubbell CL, Reid LD (1998) Isradipine combined with naltrexone persistently reduces the reward-relevant effects of cocaine and alcohol. Pharmacol Biochem Behav 60: 345–356

    PubMed  CAS  Google Scholar 

  58. Gardell LR, Hubbell CL, Reid LD (1996) Naltrexone persistently reduces rats’ intake of a palatable alcoholic beverage. Alcohol Clin Exp Res 20: 584–588

    PubMed  CAS  Google Scholar 

  59. Reid LD, Gardell LR, Chattopadhyay S, Hubbell CL (1996) Periodic naltrexone and propensity to take alcoholic beverage. Alcohol Clin Exp Res 20: 1329–1334

    PubMed  CAS  Google Scholar 

  60. Davidson D, Amit Z (1997) Naltrexone blocks acquisition of voluntary ethanol intake in rats. Alcohol Clin Exp Res 21: 677–683

    PubMed  CAS  Google Scholar 

  61. Katner SN, Magalong JG, Weiss F (1999) Reinstatement of alcohol-seeking behavior by drug-associated discriminative stimuli after prolonged extinction in the rat. Neuropsychopharmacology 20: 471–479

    Article  PubMed  CAS  Google Scholar 

  62. Le AD, Poulos CX, Harding S, Watchus J, Juzytsch W, Shaham Y (1999) Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress. Neuropsychopharmacology 21: 435–444

    PubMed  CAS  Google Scholar 

  63. Ciccocioppo R, Martin-Fardon R, Weiss F (2002) Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 27: 391–399

    Article  PubMed  CAS  Google Scholar 

  64. 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: 7856–7861

    PubMed  CAS  Google Scholar 

  65. Holtzman SG (1975) Effects of narcotic antagonists on fluid intake in the rat. Life Sci 16: 1465–1470

    Article  PubMed  CAS  Google Scholar 

  66. Brown DR, Holtzman SG (1980) Evidence that opiate receptors mediate suppression of hypertonic saline-induced drinking in the mouse by narcotic antagonists. Life Sci 26: 1543–1550

    PubMed  CAS  Google Scholar 

  67. Apfelbaum M, Mandenoff A (1981) Naltrexone suppresses hyperphagia induced in the rat by a highly palatable diet. Pharmacol Biochem Behav 15: 89–91

    Article  PubMed  CAS  Google Scholar 

  68. Goldberg SR, Morse WH, Goldberg DM (1981) Acute and chronic effects of naltrexone and naloxone on schedule-controlled behavior of squirrel monkeys and pigeons. J Pharmacol Exp Ther 216: 500–509

    PubMed  CAS  Google Scholar 

  69. Lowy MT, Yim GK (1981) The anorexic effect of naltrexone is independent of its suppressant effect on water intake. Neuropharmacology 20: 883–886

    Article  PubMed  CAS  Google Scholar 

  70. Lang IM, Strahlendorf JC, Strahlendorf HK, Lutherer LO, Barnes CD (1982) The effects of chronic administration of naltrexone on appetite and water exchange in rats. Pharmacol Biochem Behav 16: 909–913

    Article  PubMed  CAS  Google Scholar 

  71. Sanger DJ, McCarthy PS (1982) A comparison of the effects of opiate antagonists on operant and ingestive behavior. Pharmacol Biochem Behav 16: 1013–1015

    Article  PubMed  CAS  Google Scholar 

  72. Lankford MF, Myers RD (1996) Opiate and 5-HT2A receptors in alcohol drinking: preference in HAD rats is inhibited by combination treatment with naltrexone and amperozide. Alcohol 13: 53–57

    PubMed  CAS  Google Scholar 

  73. Stromberg MF, Sengpiel T, Mackler SA, Volpicelli JR, O’Brien CP, Vogel WH (2002) Effect of naltrexone on oral consumption of concurrently available ethanol and cocaine in the rat. Alcohol 28: 169–179

    Article  PubMed  CAS  Google Scholar 

  74. Mhatre M, Pruthi R, Hensley K, Holloway F (2004) 5-HT3 antagonist ICS 205–930 enhances naltrexon’s effects on ethanol intake. Eur J Pharmacol 491: 149–156

    Article  PubMed  CAS  Google Scholar 

  75. Kiianmaa K, Hoffman PL, Tabakoff B (1983) Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c, C57BL/6, and DBA/2 mice. Psychopharmacology (Berl) 79: 291–294

    CAS  Google Scholar 

  76. Hill KG, Kiefer SW (1997) Naltrexone treatment increases the aversiveness of alcohol for outbred rats. Alcohol Clin Exp Res 21: 637–641

    PubMed  CAS  Google Scholar 

  77. Ferraro FM,3rd, Hill KG, Kaczmarek HJ, Coonfield DL, Kiefer SW (2002) Naltrexone modifies the palatability of basic tastes and alcohol in outbred male rats. Alcohol 27: 107–114

    Article  PubMed  CAS  Google Scholar 

  78. Linseman MA (1989) Central versus peripheral mediation of opioid effects on alcohol consumption in free-feeding rats. Pharmacol Biochem Behav 33: 407–413

    Article  PubMed  CAS  Google Scholar 

  79. Linseman MA, Le AD (1997) Effects of opioids on the absorption of alcohol. Pharmacol Biochem Behav 58: 79–84

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Howard Florey Institute, University of Melbourne, VIC, 3010, Australia

    Michael S. Cowen

Authors
  1. Michael S. Cowen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung für Psychopharmakologie, Universit ät Heidelberg, J5, Zentralinstitut für Seelische Gesundheit, 68159, Mannheim, Germany

    Rainer Spanagel

  2. Klinik für Abhängiges Verhalten und Suchtmedizin, J5, Zentralinstitut für Seelische Gesundheit, 68159, Mannheim, Germany

    Karl F. Mann

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Cowen, M.S. (2005). Naltrexone: preclinical data. In: Spanagel, R., Mann, K.F. (eds) Drugs for Relapse Prevention of Alcoholism. Milestones in Drug Therapy MDT. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7305-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation