Psychopharmacology

, Volume 192, Issue 2, pp 207–217

Acute effects of Naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice

  • N. K. Kamdar
  • S. A. Miller
  • Y. M. Syed
  • R. Bhayana
  • T. Gupta
  • J. S. Rhodes
Original Investigation

Abstract

Rationale

Recently, a simple procedure was described, drinking in the dark (DID), in which C57BL/6J mice self-administer ethanol to the point of intoxication. The test consists of replacing the water with 20% ethanol in the home cage for 2 or 4 h early during the dark phase of the light/dark cycle.

Objectives

To determine whether the model displays predictive validity with naltrexone, and whether opioid or dopaminergic mechanisms mediate excessive drinking in the model.

Materials and methods

Naltrexone or GBR 12909 were administered via intraperitoneal injections immediately before offering ethanol solutions, plain tap water, or 10% sugar water to male C57BL/6J mice, and consumption was monitored over a 2- or 4-h period using the DID procedure.

Results

Naltrexone (0.5, 1, or 2 mg/kg) dose dependently decreased ethanol drinking but these same doses had no significant effect on the consumption of plain water or 10% sugar water. GBR 12909 (5, 10, and 20 mg/kg) dose dependently reduced the consumption of ethanol and sugar water but had no effect on plain water drinking.

Conclusions

The DID model demonstrates predictive validity. Both opioid and dopamine signaling are involved in ethanol drinking to intoxication. Different physiological pathways mediate high ethanol drinking as compared to water or sugar water drinking in DID. DID may be a useful screening tool to find new alcoholism medications and to discover genetic and neurobiological mechanisms relevant to the human disorder.

Keywords

Alcoholism Naltrexone GBR 12909 Ethanol C57BL/6J Drinking Natural reward Water Opioid Dopamine 

References

  1. Aalto J, Kiianmaa K (1986) REM-sleep deprivation-induced increase in ethanol intake: role of brain monoaminergic neurons. Alcohol 3:377–81PubMedCrossRefGoogle Scholar
  2. Aalto J, Kiianmaa K (1987) Role of brain monoaminergic systems in the increased ethanol drinking caused by REM-sleep deprivation. Alcohol Alcohol Suppl 1:313–317PubMedGoogle Scholar
  3. Andersen PH (1989) The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 166:493–504PubMedCrossRefGoogle Scholar
  4. Avena NM, Rada P, Moise N, Hoebel BG (2006) Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response. Neuroscience 139:813–820PubMedCrossRefGoogle Scholar
  5. Baunez C, Dias C, Cador M, Amalric M (2005) The subthalamic nucleus exerts opposite control on cocaine and ‘natural’ rewards. Nat Neurosci 8:484–489PubMedGoogle Scholar
  6. Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510PubMedCrossRefGoogle Scholar
  7. 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 22:359–366PubMedGoogle Scholar
  8. Brewer C (1995) Naltrexone in alcohol dependence. Lancet 346:1374PubMedCrossRefGoogle Scholar
  9. Carelli RM, Wondolowski J (2003) Selective encoding of cocaine versus natural rewards by nucleus accumbens neurons is not related to chronic drug exposure. J Neurosci 23:11214–11223PubMedGoogle Scholar
  10. Carelli RM, Ijames SG, Crumling AJ (2000) Evidence that separate neural circuits in the nucleus accumbens encode cocaine versus “natural” (water and food) reward. J Neurosci 20:4255–4266PubMedGoogle Scholar
  11. Cicero T (1980) Alcohol self-administration, tolerance and withdrawal in humans and animals: theoretical and methodological issues. In: Rigter H, Crabbe JC (eds) Alcohol tolerance and dependence. Elsevier, Amsterdam, pp 1–51Google Scholar
  12. 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 26:43–47PubMedCrossRefGoogle Scholar
  13. Coonfield DL, Kiefer SW, Ferraro FM, 3rd, Sinclair JD (2004) Ethanol palatability and consumption by high ethanol-drinking rats: manipulation of the opioid system with naltrexone. Behav Neurosci 118:1089–1096PubMedCrossRefGoogle Scholar
  14. Crabbe JC, Belknap JK, Buck KJ (1994) Genetic animal models of alcohol and drug abuse. Science 264:1715–1723PubMedCrossRefGoogle Scholar
  15. Cunningham CL, Fidler TL, Hill KG (2000) Animal models of alcohol’s motivational effects. Alcohol Res Health 24:85–92PubMedGoogle Scholar
  16. Davidson D, Amit Z (1997) Naltrexone blocks acquisition of voluntary ethanol intake in rats. Alcohol Clin Exp Res 21:677–683PubMedGoogle Scholar
  17. De Sousa A (2004) A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol dependence. Alcohol Alcohol 39:528–531PubMedGoogle Scholar
  18. Di Chiara G, Acquas E, Tanda G, Cadoni C (1993) Drugs of abuse: biochemical surrogates of specific aspects of natural reward? Biochem Soc Symp 59:65–81PubMedGoogle Scholar
  19. Dole VP, Gentry RT (1984) Toward an analogue of alcoholism in mice: scale factors in the model. Proc Natl Acad Sci USA 81:3543–3546PubMedCrossRefGoogle Scholar
  20. Egli M (2005) Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism? Addict Biol 10:309–319PubMedCrossRefGoogle Scholar
  21. Engleman EA, McBride WJ, Wilber AA, Shaikh SR, Eha RD, Lumeng L, Li TK, Murphy JM (2000) Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats: effects on dialysate dopamine levels and ethanol intake. Alcohol Clin Exp Res 24:795–801PubMedCrossRefGoogle Scholar
  22. Escher T, Mittleman G (2006) Schedule-induced alcohol drinking: non-selective effects of acamprosate and naltrexone. Addict Biol 11:55–63PubMedCrossRefGoogle Scholar
  23. Fachin-Scheit DJ, Frozino Ribeiro A, Pigatto G, Oliveira Goeldner F, Boerngen de Lacerda R (2006) Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving. J Neural Transm 113: 1305–1321PubMedCrossRefGoogle Scholar
  24. Finn DA, Belknap JK, Cronise K, Yoneyama N, Murillo A, Crabbe JC (2005) A procedure to produce high alcohol intake in mice. Psychopharmacology 178:471–480PubMedCrossRefGoogle Scholar
  25. Froehlich JC (1996) The neurobiology of ethanol-opioid interactions in ethanol reinforcement. Alcohol Clin Exp Res 20:181A–186APubMedCrossRefGoogle Scholar
  26. Froehlich JC, Li TK (1994) Opioid involvement in alcohol drinking. Ann NY Acad Sci 739:156–167PubMedCrossRefGoogle Scholar
  27. Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere RB, Lee KK, Lowenstam I et al (1986) Disulfiram treatment of alcoholism. A veterans administration cooperative study. Jama 256:1449–1455PubMedCrossRefGoogle Scholar
  28. Goodwin FL, Campisi M, Babinska I, Amit Z (2001) Effects of naltrexone on the intake of ethanol and flavored solutions in rats. Alcohol 25:9–19PubMedCrossRefGoogle Scholar
  29. Hodge CW, Miles MF, Sharko AC, Stevenson RA, Hillmann JR, Lepoutre V, Besheer J, Schroeder JP (2006) The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology 183:429–438PubMedCrossRefGoogle Scholar
  30. Kelley AE, Berridge KC (2002) The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci 22:3306–3311PubMedGoogle Scholar
  31. Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, Kampf P, Stracke R, Baehr M, Naber D, Wiedemann K (2003) Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 60:92–99PubMedCrossRefGoogle Scholar
  32. 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 104:367–376PubMedCrossRefGoogle Scholar
  33. Kranzler HR, Burleson JA, Korner P, Del Boca FK, Bohn MJ, Brown J, Liebowitz N (1995) Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics. Am J Psychiatry 152:391–397PubMedGoogle Scholar
  34. Le AD, Poulos CX, Quan B, Chow S (1993) The effects of selective blockade of delta and mu opiate receptors on ethanol consumption by C57BL/6 mice in a restricted access paradigm. Brain Res 630:330–332PubMedCrossRefGoogle Scholar
  35. Li G, Rhodes JS, Girard I, Gammie SC, Garland T Jr (2004) Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running. Physiol Behav 83:515–524PubMedCrossRefGoogle Scholar
  36. McBride WJ, Chernet E, Dyr W, Lumeng L, Li TK (1993) Densities of dopamine D2 receptors are reduced in CNS regions of alcohol-preferring P rats. Alcohol 10:387–390PubMedCrossRefGoogle Scholar
  37. McBride WJ, Chernet E, Russell RN, Chamberlain JK, Lumeng L, Li TK (1997) Regional CNS densities of serotonin and dopamine receptors in high alcohol-drinking (HAD) and low alcohol-drinking (LAD) rats. Alcohol 14:603–609PubMedCrossRefGoogle Scholar
  38. McClearn G, Rodgers D (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:691–695Google Scholar
  39. Melendez RI, Rodd-Henricks ZA, Engleman EA, Li TK, McBride WJ, Murphy JM (2002) Microdialysis of dopamine in the nucleus accumbens of alcohol-preferring (P) rats during anticipation and operant self-administration of ethanol. Alcohol Clin Exp Res 26:318–325PubMedGoogle Scholar
  40. Middaugh LD, Bandy AL (2000) Naltrexone effects on ethanol consumption and response to ethanol conditioned cues in C57BL/6 mice. Psychopharmacology 151:321–327PubMedCrossRefGoogle Scholar
  41. Middaugh LD, Lee AM, Bandy AL (2000) Ethanol reinforcement in nondeprived mice: effects of abstinence and naltrexone. Alcohol Clin Exp Res 24:1172–1179PubMedCrossRefGoogle Scholar
  42. Middaugh LD, Szumlinski KK, Van Patten Y, Marlowe AL, Kalivas PW (2003) Chronic ethanol consumption by C57BL/6 mice promotes tolerance to its interoceptive cues and increases extracellular dopamine, an effect blocked by naltrexone. Alcohol Clin Exp Res 27:1892–1900PubMedCrossRefGoogle Scholar
  43. Murphy JM, McBride WJ, Lumeng L, Li TK (1988) Effects of serotonin and sopamine agents on ethanol intake of alcohol-preferring P rats. Alcohol Clin Exp Res 12:306AGoogle Scholar
  44. Ng GY, George SR (1994) Dopamine receptor agonist reduces ethanol self-administration in the ethanol-preferring C57BL/6J inbred mouse. Eur J Pharmacol 269:365–374PubMedCrossRefGoogle Scholar
  45. Ng GY, O’Dowd BF, George SR (1994) Genotypic differences in brain dopamine receptor function in the DBA/2J and C57BL/6J inbred mouse strains. Eur J Pharmacol 269:349–364PubMedCrossRefGoogle Scholar
  46. Parkes H, Sinclair JD (2000) Reduction of alcohol drinking and upregulation of opioid receptors by oral naltrexone in AA rats. Alcohol 21:215–221PubMedCrossRefGoogle Scholar
  47. 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 21:691–702PubMedGoogle Scholar
  48. Preti A (2000) Vanoxerine National Institute on Drug Abuse. Curr Opin Investig Drugs 1:241–251PubMedGoogle Scholar
  49. Rhodes JS, Hosack GR, Girard I, Kelley AE, Mitchell GS, Garland T Jr (2001) Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology 158:120–131PubMedCrossRefGoogle Scholar
  50. Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav 84:53–63PubMedCrossRefGoogle Scholar
  51. Rhodes JS, Ford MM, Yu C-H, Brown LL, Finn DA, Garland T Jr, Crabbe JC (2007) Mouse inbred strain differences in ethanol drinking to intoxication. Genes, Brain and Behavior 6:1–18CrossRefGoogle Scholar
  52. Sharpe AL, Samson HH (2001) Effect of naloxone on appetitive and consummatory phases of ethanol self-administration. Alcohol Clin Exp Res 25:1006–1011PubMedCrossRefGoogle Scholar
  53. Stefanini E, Frau M, Garau MG, Garau B, Fadda F, Gessa GL (1992) Alcohol-preferring rats have fewer dopamine D2 receptors in the limbic system. Alcohol Alcohol 27:127–130PubMedGoogle Scholar
  54. Tupala E, Tiihonen J (2004) Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry 28:1221–1247PubMedCrossRefGoogle Scholar
  55. van der Hoek GA, Cooper SJ (1994) The selective dopamine uptake inhibitor GBR 12909: its effects on the microstructure of feeding in rats. Pharmacol Biochem Behav 48:135–140PubMedCrossRefGoogle Scholar
  56. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880PubMedGoogle Scholar
  57. Wise RA (2002) Brain reward circuitry: insights from unsensed incentives. Neuron 36:229–240PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • N. K. Kamdar
    • 1
    • 2
  • S. A. Miller
    • 1
    • 2
  • Y. M. Syed
    • 1
    • 2
  • R. Bhayana
    • 1
    • 2
  • T. Gupta
    • 1
    • 2
  • J. S. Rhodes
    • 1
    • 2
  1. 1.Department of PsychologyBeckman InstituteUrbanaUSA
  2. 2.University of Illinois at Urbana–ChampaignUrbanaUSA

Personalised recommendations