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Animal Models of Motivation for Drinking in Rodents with a Focus on Opioid Receptor Neuropharmacology

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Recent Developments in Alcoholism

Part of the book series: Recent Developments in Alcoholism ((RDIA,volume 16))

Summary and Conclusions

Ethanol, like other drugs of abuse, has motivating properties that can be developed as animal models of self-administration. A major strength of the operant approach where an animal must work to obtain ethanol is that it reduces confounds due to palatability and controls for nonspecific malaise-inducing effects. In the domain of opioid peptide systems, limited access paradigms have good predictive validity. In addition, animal models of excessive drinking—either environmentally or genetically induced—also appear sensitive to blockade or inactivation of opioid peptide receptors. Ethanol availability can be predicted by cues associated with positive reinforcement, and these models are sensitive to the administration of opioid antagonists. Perhaps most exciting are the recent results suggesting that the key element in opioid peptide systems that is important for the positive reinforcing effects of ethanol is the μ-opioid receptor. How exactly ethanol modulates μ-receptor function will be a major challenge of future research. Nevertheless, the apparently critical role of the μ receptor in ethanol reinforcement refocuses the neuropharmacology of ethanol reinforcement in the opioid peptide domain and opens a novel avenue for exploring medications for treating alcoholism.

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References

  • Belknap, J.K., Crabbe, J.C., & Young, E.R. (1993). Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112, 503–510.

    PubMed  Google Scholar 

  • Biggs, T.A., & Myers, R.D. (1998). Naltrexone and amperozide modify chocolate and saccharin drinking in high alcohol-preferring P rats. Pharmacology Biochemistry and Behavior 60, 407–413.

    Article  Google Scholar 

  • Charness, M.E. (1989). Ethanol and opioid receptor signalling. Experientia 45, 418–428.

    Article  PubMed  Google Scholar 

  • Ciccocioppo, R., Angeletti, S., & Weiss, F. (2001). Long-lasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: Role ofgenetic ethanol preference. Alcoholism: Clinical and Experimental Research 25, 1414–1419.

    Google Scholar 

  • Ciccocioppo, R., Martin-Fardon, R., & Weiss, F. (2002). Effect of selective blockade of μ1 or δ opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology, 27, 391–399.

    Article  PubMed  Google Scholar 

  • Cicero, T.J. (1979). A critique of animal analogs of alcoholism. In E. Majchrowicz & E.P. Noble (eds.), Biochemistry and Pharmacology of Ethanol, vol. 2. New York: Plenum Press, pp. 533–560.

    Google Scholar 

  • Corbett, A.D., Paterson, S.J., & Kosterlitz, H.W. (1993). Selectivity of ligands for opioid receptors. In A. Herz (ed.), Opioids I (series title: Handbook of Experimental Pharmacology, vol. 104/1). Berlin: Springer-Verlag, pp. 645–673.

    Google Scholar 

  • Crabbe, J.C., Phillips, T.J., Cunningham, C.L., & Belknap, J.K. (1992). Genetic determinants of ethanol reinforcement. In P.W. Kalivas & H.H. Samson (eds.), The Neurobiology of Drug and Alcohol Addiction (series title: Annals of the New York Academy of Sciences, vol. 654). New York: New York Academy of Sciences, pp. 302–310.

    Google Scholar 

  • Cunningham, C.L., Fidler, T.L., & Hill, K.G. (2000). Animal models of alcohoľs motivational effects. Alcohol Research and Health 24, 85–92.

    PubMed  Google Scholar 

  • Di Chiara, G., Acquas, E., & Tanda, G. (1996). Ethanol as a neurochemical surrogate of conventional reinforcers: The dopamine-opioid link. Alcohol 13, 13–17.

    PubMed  Google Scholar 

  • Elmer, G.I., Meisch, R.A., & George, F.R. (1986). Oral ethanol reinforced behavior in inbred mice. Pharmacology Biochemistry and Behavior 24, 1417–1421.

    Article  Google Scholar 

  • Elmer, G.I., Meisch, R.A., & George, F.R. (1987). Differential concentration-response curves for oral ethanol self-administration in C57BL/6J and BALB/cJ mice. Alcohol 4, 63–68.

    Article  PubMed  Google Scholar 

  • Filliol, D., Ghozland, S., Chluba, J., Martin, M., Matthes, H.W.D., Simonin, F., Befort, K., Gaveriaux-Ruff, C., Dierich, A., LeMeur, M., Valverde, O., Maldonado, R., & Kieffer, B.L. (2000). Mice deficient for delta-and mu-opioid receptors exhibit opposing alterations of emotional responses. Nature Genetics 25, 195–200.

    PubMed  Google Scholar 

  • Franck, J., Lindholm, S., & Raaschou, P. (1998). Modulation of volitional ethanol intake in the rat by central delta-opioid receptors. Alcoholism: Clinical and Experimental Research 22, 1185–1189.

    Google Scholar 

  • Froehlich, J.C. (1995). Genetic factors in alcohol self-administration. Journal of Clinical Psychiatry 56 (Suppl. 7), 15–23.

    PubMed  Google Scholar 

  • Froehlich, J.C., Zweifel, M., Harts, J., Lumeng, L., & Li, T.-K. (1991). Importance of delta opioid receptors in maintaining high alcohol drinking, Psychopharmacology 103, 467–472.

    Article  PubMed  Google Scholar 

  • Gauvin, D.V., Moore, K.R., & Holloway, F.A. (1993). Do rat strain differences in ethanol consumption reflect differences in ethanol sensitivity or the preparedness to learn? Alcohol 10, 37–43.

    Article  PubMed  Google Scholar 

  • Grahame, N.J., Li, T.K., & Lumeng, L. (1999). Selective breeding for high and low alcohol preference in mice. Behavior Genetics 29, 47–57.

    Article  PubMed  Google Scholar 

  • Heyser, C.J., Moc, K., Roberts, A.J., & Koob, G.F. (2000). The effects of chronic naltrexone, acamprosate and the combination on the alcohol deprivation effect in rats. Alcoholism: Clinical and Experimental Research 24 (5 Suppl.), 14A.

    Google Scholar 

  • Heyser, C.J., Schulteis, G., Durbin, P., & Koob, G.F. (1998). Chronic acamprosate eliminates the alcohol deprivation effect while having limited effects on baseline responding for ethanol in rats. Neuropsychopharmacology 18, 125–133.

    Article  PubMed  Google Scholar 

  • Heyser, C.J., Schulteis, G., & Koob, G.F. (1997). Increased ethanol self-administration following a period of imposed ethanol deprivation in rats trained in a limited access paradigm. Alcoholism: Clinical and Experimental Research 21, 784–791.

    Google Scholar 

  • Honkanen, A., Vilamo, L., Wegelius, K., Sarviharju, M., Hyytïa, P., & Korpi, E.R. (1996). Alcohol drinking is reduced by a μ1-but not by a δ-opioid receptor antagonist in alcohol-preferring rats. European Journal of Pharmacology 304, 7–13.

    Article  PubMed  Google Scholar 

  • Hyytia, P. (1993). Involvement of μ-opioid receptors in alcohol drinking by alcohol-preferring AA rats. Pharmacology Biochemistry and Behavior 45, 697–701.

    Article  Google Scholar 

  • Hyytia, P., & Kiianmaa, K. (2001). Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats. Alcoholism: Clinical and Experimental Research 25, 25–33.

    Google Scholar 

  • Hyytia, P., & Sinclair, J.D. (1993). Responding for oral ethanol after naloxone treatment by alcohol-preferring AA rats. Alcoholism: Clinical and Experimental Research 17, 631–636.

    Google Scholar 

  • Jackson, H.C., Ripley, T.L., & Nutt, D.J. (1989). Exploring delta-receptor function using the selective opioid antagonist naltrindole. Neuropharmacology 28, 1427–1430.

    PubMed  Google Scholar 

  • June, H.L., Grey, C., Warren-Reese, C., Durr, L.F., Ricks-Cord, A., Johnson, A., McCane, S., Williams, L.S., Mason, D., Cummings, R., & Lawrence, A. (1998). The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: Preclinical studies in ethanol-preferring and outbred Wistar rats. Alcoholism: Clinical and Experimental Research 22, 2174–2185.

    Google Scholar 

  • June, H.L., McCane, S.R., Zink, R.W., Portoghese, P.S., Li, T.K., & Froehlich, J.C. (1999). The delta 2-opioid receptor antagonist naltriben reduces motivated responding for ethanol. Psychopharmacology 147, 81–89.

    Article  PubMed  Google Scholar 

  • Katner, S.N., Magalong, J.G., & 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  Google Scholar 

  • Katner, S.N., & Weiss, F. (1999). Ethanol-associated olfactory stimuli reinstate ethanol-seeking behavior after extinction and modify extracellular dopamine levels in the nucleus accumbens. Alcoholism: Clinical and Experimental Research 23, 1751–1760.

    Google Scholar 

  • Krishnan-Sarin, S., Jing, S.L., Kurtz, D.L., Zweifel, M., Portoghese, P.S., Li, T.K., & Froehlich, J.C. (1995a). The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference. Psychopharmaacology 120, 177–185.

    Google Scholar 

  • Krishnan-Sarin, S., Portoghese, P.S., Li, T.-K., & Froehlich, J.C. (1995b). The delta2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference. Pharmacology Biochemistry and Behavior 52, 153–159.

    Article  Google Scholar 

  • Krishnan-Sarin, S., Wand, G.S., Li, X.W., Portoghese, P.S., & Froehlich, J.C. (1998). Effect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking. Pharmacology Biochemistry and Behavior 59, 627–635.

    Article  Google Scholar 

  • Le, A.D., Poulos, C.X., 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 Research 630, 330–332.

    PubMed  Google Scholar 

  • Li, T.K., Lumeng, L., & Doolittle, D.P. (1993). Selective breeding for alcohol preference and associated responses. Behavior Genetics 23, 163–170.

    Article  PubMed  Google Scholar 

  • Ludwig, A.M., & Stark, L.H. (1974). Alcohol craving. Quarterly Journal of Studies on Alcohol 35, 899–905.

    PubMed  Google Scholar 

  • Matthes, H.W.D., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I., Befort, K., Dierich, A., Le Meur, M., Dollé, P., Tzavara, E., Hanoune, J., Roques, B.P., & Kieffer, B.L. (1996). Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the μ-opioid-receptor gene. Nature 383, 819–823.

    Article  PubMed  Google Scholar 

  • McBride, W.J., & Li, T.K. (1998). Animal models of alcoholism: Neurobiology of high alcohol-drinking behavior in rodents. Critical Reviews in Neurobiology 12, 339–369.

    PubMed  Google Scholar 

  • Meisch, R.A. (1984). Alcohol self-administration by experimental animals. In R.G. Smart, H.D. Cappell, F. B. Glaser, Y. Israel, H. Kalant, W. Schmidt, & E. M. Sellers (eds.), Research Advances in Alcohol and Drug Problems, Vol. 8. New York: Plenum Press, pp. 23–45.

    Google Scholar 

  • Middaugh, L.D., Kelley, B.M., Cuison, E.R. Jr., & Groseclose, C.H. (1999). Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice. Alcoholism: Clinical and Experimental Research 23, 456–464.

    Google Scholar 

  • Middaugh, L.D., Kelley, B.M., Groseclose, C.H., & Cuison, E.R. Jr. (2000). Delta-opioid and 5-HT3 receptor antagonist effects on ethanol reward and discrimination in C57BL/6 mice. Pharmacology Biochemistry and Behavior 65, 145–154.

    Article  Google Scholar 

  • O’Malley, S., Jaffe, A.J., Chang, G., Schottenfeld, R.S., Meyer, R.E., & Rounsaville, B. (1992). Naltrexone and coping skills therapy for alcohol dependence: A controlled study. Archives of General Psychiatry 49, 881–887.

    Google Scholar 

  • Rassnick, S., Pulvirenti, L., & Koob, G.F. (1993). SDZ 205,152, a novel dopamine receptor agonist, reduces oral ethanol self-administration in rats. Alcohol 10, 127–132.

    Article  PubMed  Google Scholar 

  • Raynor, K., Kong, H., Chen, Y., Yasuda, K., Yu, L., Bell, G.I., & Reisine, T. (1994). Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Molecular Pharmacology 45, 330–334.

    PubMed  Google Scholar 

  • Reid, L.D., & Hunter, G.A. (1984). Morphine and naloxone modulate intake of ethanol. Alcohol 1, 33–37.

    Article  PubMed  Google Scholar 

  • Risinger, F.O., Brown, M.M., Doan, A.M., & Oakes, R.A. (1998). Mouse strain differences in oral operant ethanol reinforcement under continuous access conditions. Alcoholism: Clinical and Experimental Research 22, 677–684.

    Google Scholar 

  • Robbins, S.J., & Ehrman, R.N. (1992). Designing studies of drug conditioning in humans. Psychopharmacology 106, 143–153.

    PubMed  Google Scholar 

  • Roberts, A.J., Gold, L.H., Polis, I., McDonald, J.S., Filliol, D., Kieffer, B.L., & Koob, G.F. (2001). Increased ethanol self-administration in ∂-receptor knockout mice. Alcoholism: Clinical and Experimental Research 25, 1249–1256.

    Google Scholar 

  • Roberts, A.J., Heyser, C.J., & Koob, G.F. (1999). Operant self-administration of sweetened versus unsweetened ethanol: Effects on blood alcohol levels. Alcoholism: Clinical and Experimental Research 23, 1151–1157.

    Google Scholar 

  • Roberts, A.J., McDonald, J.S., Heyser, C.J., Kieffer, B.L., Matthes, H.W.D., Koob, G.F., & Gold, L.H. (2000). μ-Opioid receptor knockout mice do not self-administer alcohol. Journal of Pharmacology and Experimental Therapeutics 293, 1002–1008.

    PubMed  Google Scholar 

  • Rodefer, J.S., Campbell, U.C., Cosgrove, K.P., & Carroll, M.E. (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  Google Scholar 

  • Samson, H.H. (1986). Initiation of ethanol reinforcement using a sucrose-substitution procedure in food-and water-sated rats. Alcoholism: Clinical and Experimental Research 10, 436–442.

    Google Scholar 

  • Samson, H.H. (1987). Initiation of ethanol-maintained behavior: A comparison of animal models and their implication to human drinking. In T. Thompson, P.B. Dews, & J.E. Barrett (eds.), Neurobehavioral Pharmacology (series title: Advances in Behavioral Pharmacology, Vol. 6). Hillsdale NJ: Erlbaum, pp. 221–248.

    Google Scholar 

  • Sinclair, J.D. (1979). Alcohol-deprivation effect in rats genetically selected for their ethanol preference. Pharmacology Biochemistry and Behavior 10, 597–602.

    Article  Google Scholar 

  • Sinclair, J.D., & Senter, R.J. (1967). Increased preference for ethanol in rats following alcohol deprivation. Psychonomic Science 8, 11–12.

    Google Scholar 

  • Sinclair, J.D., & Senter, R.J. (1968). Development of an alcohol-deprivation effect in rats. Quarterly Journal of Studies on Alcohol 29, 863–867.

    PubMed  Google Scholar 

  • Spanagel, R., & Holter, S.M. (1999) Long-term alcohol self-administration with repeated alcohol deprivation phases: An animal model of alcoholism? Alcohol and Alcoholism 34, 231–243.

    Article  PubMed  Google Scholar 

  • Spanagel, R., Holter, S.M., Allingham, K., Landgraf, R., & Zieglgansberger, W. (1996). Acamprosate and alcohol: I.Effects on alcohol intake following alcohol deprivation in the rat. European Journal of Pharmacology 305, 39–44.

    PubMed  Google Scholar 

  • Stromberg, M.F., Casale, M., Volpicelli, L., Volpicelli, J.R., & O’Brien, C.P. (1998). A comparison of the effects of the opioid antagonists naltrexone, naltrindole, and ß-funaltrexamine on ethanol consumption in the rat. Alcohol 15, 281–289.

    Article  PubMed  Google Scholar 

  • Stromberg, M.F., Mackler, S.A., Volpicelli, J.R., & O’Brien, C.P. (2001). Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption. Alcohol 23, 109–116.

    Article  PubMed  Google Scholar 

  • Takemori, A.E., & Portoghese, P.S. (1992). Selective naltrexone-derived opioid receptor antagonists. Annual Review of Pharmacology and Toxicology 32, 239–269.

    Article  PubMed  Google Scholar 

  • Ulm, R.R., Volpicelli, J.R., & Volpicelli, L.A. (1995). Opiates and alcohol self-administration in animals. Journal of Clinical Psychiatry 56(Suppl. 7), 5–14.

    PubMed  Google Scholar 

  • Veale, W.L. (1973). Ethanol selection in the rat following forced acclimation. Pharmacology Biochemistry and Behavior 1, 233–235.

    Google Scholar 

  • Volpicelli, J.R., Alterman, A.I., Hayashida, M., & O’Brien, C.P. (1992). Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry 49, 876–880.

    PubMed  Google Scholar 

  • Wehner, J.M., & Bowers, B.J. (1995). Use of transgenics, null mutants, and antisense approaches to study ethanoľs actions. Alcoholism: Clinical and Experimental Research 19, 811–820.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Williams, K.L., & Woods, J.H. (1998). Oral ethanol-reinforced responding in rhesus monkeys: Effects of opioid antagonists selective for the mu-, kappa-, or delta-receptor. Alcoholism: Clinical and Experimental Research 22, 1634–1639.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neuropharmacology, Scripps Research Institute, La Jolla, California, 92037

    George F. Koob, Amanda J. Roberts, Simon N. Katner, Roberto Ciccocioppo & Friedbert Weiss

  2. Unite Mixte de Recherche, Institut de Genetique et de Biologie Moleculaire et Cellulaire, 7104, Illkirch, France

    Brigitte L. Kieffer

  3. Department of Psychology, Franklin and Marshall College, Lancaster, Pennsylvania, 17604

    Charles J. Heyser

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  1. George F. Koob
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  2. Amanda J. Roberts
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  3. Brigitte L. Kieffer
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  4. Charles J. Heyser
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  5. Simon N. Katner
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  6. Roberto Ciccocioppo
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  7. Friedbert Weiss
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  1. New York University School of Medicine, New York, New York

    Marc Galanter

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Koob, G.F. et al. (2002). Animal Models of Motivation for Drinking in Rodents with a Focus on Opioid Receptor Neuropharmacology. In: Galanter, M., et al. Recent Developments in Alcoholism. Recent Developments in Alcoholism, vol 16. Springer, Boston, MA. https://doi.org/10.1007/0-306-47939-7_19

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  • DOI: https://doi.org/10.1007/0-306-47939-7_19

  • Publisher Name: Springer, Boston, MA

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