Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-28T08:44:24.220Z Has data issue: false hasContentIssue false

Morphine dependent behaviour in rats: some clinical implications1

Published online by Cambridge University Press:  09 July 2009

R. Kumar
Affiliation:
From the Department of Pharmacology, University College London
I. P. Stolerman
Affiliation:
The Maudsley Hospital, London

Synopsis

An animal model of morphine dependence is described, in which rats learned to overcome their aversion to solutions of morphine and eventually drank such solutions in preference to water on choice trials. Selected aspects of the acquisition, maintenance, and elimination of this type of morphine dependent behaviour were studied and the findings are discussed in terms of their relevance to man.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1973

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Akera, T., and Brody, T. M. (1968). The addiction cycle to narcotics in the rat and its relation to catecholamines. Biochemical Pharmacology, 17, 675688.CrossRefGoogle ScholarPubMed
Bewley, T. H. (1968). Recent changes in the incidence in all types of drug dependence in Great Britain. Proceedings of the Royal Society of Medicine, 62, 175177.CrossRefGoogle Scholar
Broadhurst, P. L. (1966). Behavioral inheritance: past and present. Conditional Reflex, 1, 315.Google Scholar
Cappell, H., and LeBlanc, A. E. (1971). Some factors controlling oral morphine intake in rats. Psychopharmacologia, 21, 192211.Google Scholar
Chein, I. (1969). Psychological functions of drug use. In Scientific Basis of Drug Dependence. A Symposium, pp. 1330. Edited by Steinberg, H.. Churchill: London.Google Scholar
Clark, R., and Polish, E. (1960). Avoidance conditioning and alcohol consumption in rhesus monkeys. Science, 132, 223224.Google Scholar
Cochin, J., and Kornetsky, C. (1961). Development and loss of tolerance to morphine in the rat after single and multiple injections. Journal of Pharmacology and Experimental Therapeutics, 145, 110.Google Scholar
Collier, H. O. J. (1969). Humoral transmitters, supersensitivity, receptors and dependence. In Scientific Basis of Drug Dependence. A Symposium, pp. 4966. Edited by Steinberg, H.. Churchill: London.Google Scholar
Connell, P. H. (1969). Drug dependence in Great Britain: a challenge to the practice of medicine. In Scientific Basis of Drug Dependence. A Symposium, pp. 291299. Edited by Steinberg, H.. Churchill: London.Google Scholar
Davis, J. D., and Miller, N. E. (1963). Fear and pain: their effect on self-injection of amobarbital sodium by rats. Science, 141, 12861287.CrossRefGoogle ScholarPubMed
Davis, J. D., Lulenski, G. C., and Miller, N. E. (1968). Comparative studies of barbiturate self-administration. International Journal of the Addictions, 3, 207214.CrossRefGoogle Scholar
Deneau, G. A. (1969). Psychogenic dependence in monkeys. In Scientific Basis of Drug Dependence. A Symposium, pp. 199207. Edited by Steinberg, H.. Churchill: London.Google Scholar
Deneau, G., Yanagita, T., and Seevers, M. H. (1969). Self-administration of psychoactive substances by the monkey. Psychopharmacologia, 16, 3048.Google Scholar
Edwards, G. (1970). Place of treatment professions in society's response to chemical abuse. British Medical Journal, 2, 195199.CrossRefGoogle ScholarPubMed
Fink, M., Zaks, A., Resnick, R., and Freedman, A. M. (1971). Opiate antagonists in the treatment of heroin dependence. In Narcotic Drugs: Biochemical Pharmacology, pp. 468477. Edited by Clouet, D. H.. Plenum Press: New York.Google Scholar
Forsyth, A. A. (1968). British Poisonous Plants. 2nd edn. Bulletin 161. Ministry of Agriculture, Fisheries and Food. H.M.S.O.: London.Google Scholar
Garcia, J., and Ervin, F. R. (1968). Gustatory-visceral and telereceptor-cutaneous conditioning—adaptation in internal and external milieus. Communications in Behaviora Biology. Part A, 1, 389415.Google Scholar
Geber, B. A. (1969). Non-dependent drug use: some psychological aspects. In Scientific Basis of Drug Dependence pp. 375393. Edited by Steinberg, H.. Churchill: London.Google Scholar
Goldberg, S. R. (1970). Relapse to opioid dependence: the role of conditioning. In Drug Dependence, pp. 170197. Edited by Harris, R. T., Mclsaac, W. M., and Schuster, C. R.. Austin: University of Texas Press.Google Scholar
Goldberg, S. R., and Schuster, C. R. (1967). Conditioned suppression by a stimulus associated with nalorphine in morphine-dependent monkeys. Journal of the Experimental Analysis of Behavior, 10, 235242.Google Scholar
Goldberg, S. R., and Schuster, C. R. (1970). Conditioned nalorphine-induced abstinence changes: persistence in post morphine-dependent monkeys. Journal of the Experimental Analysis of Behavior, 14, 3346.Google Scholar
Goldberg, S. R., Woods, J. H., and Schuster, C. R. (1971). Nalorphine-induced changes in morphine self-administration in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 176, 464471.Google ScholarPubMed
Harris, R. T., Claghorn, J. L., and Schoolar, J. C. (1968). Self administration of minor tranquilizers as a function of conditioning. Psychopharmacologia, 13, 8188.Google Scholar
Hawks, D. V. (1971). The dimensions of drug dependence in the United Kingdom. International Journal of the Addictions, 6, 135160.Google Scholar
Hawks, D., Mitcheson, M., Ogborne, A., and Edwards, G. (1969). Abuse of methylamphetamine. British Medical Journal, 2, 715721.Google Scholar
Hery, F., Pujol, J. F., Lopez, M., Macon, J., and Glowinski, J. (1970). Increased synthesis and utilization of serotonin in the central nervous system of the rat during paradoxical sleep deprivation. Brain Research, 21, 391403.CrossRefGoogle ScholarPubMed
Hore, B. D. (1971). Factors in alcoholic relapse. British Journal of Addiction, 66, 8996.Google Scholar
Jaffe, J. H. (1970). Drug addiction and drug abuse. In The Pharmacological Basis of Therapeutics, pp. 276313. 4th edn. Edited by Goodman, L. S. and Gilman, A.. Macmillan: New York.Google Scholar
Joël, E., and Ettinger, A. (1926). Zür Pathologie der Gewöhnung. III. Mitteilung; Experimentelle Studien über Morphingegewöhnung. Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie, 115, 334350.Google Scholar
Katz, D. M., and Steinberg, H. (1970). Long-term isolation in rats reduces morphine response. Nature, 228, 469471.Google Scholar
Katz, D. M., and Steinberg, H. (1972). Factors which might modify morphine dependence in rats. In Biochemical and Pharmacological Aspects of Dependence and Reports on Marihuana Research, pp. 4661. Edited by Van Praag, H. M. and DeErven, F.. Bonn, N. V.: Haarlem.Google Scholar
Khazan, N., and Colasanti, B. (1971). EEG correlates of morphine challenge in post-addict rats. Psychopharmacologia, 22, 5663.Google Scholar
Khazan, N., Weeks, J. R., and Schroeder, L. A. (1967). Electroencephalographic, electromyographic and behavioral correlates during a cycle of self-maintained morphine addiction in the rat. Journal of Pharmacology and Experimental Therapeutics, 155, 521531.Google Scholar
Kumar, R., (1972). Morphine dependence in rats: secondary reinforcement from environmental stimuli. Psychopharmacologia, 25, 332338.Google Scholar
Kumar, R., Mitchell, E., and Stolerman, I. P. (1971). Disturbed patterns of behaviour in morphine tolerant and abstinent rats. British Journal of Pharmacology, 42, 473484.CrossRefGoogle ScholarPubMed
Kumar, R., Steinberg, H., and Stolerman, I. P. (1968). Inducing a preference for morphine in rats without premedication. Nature, 218, 564565.Google Scholar
Kumar, R., Steinberg, H., and Stolerman, I. P. (1969). How rats can become dependent on morphine in the course of relieving another need. In Scientific Basis of Drug Dependence. A Symposium, pp. 209220. Edited by Steinberg, H.. Churchill: London.Google Scholar
Kumar, R., and Stolerman, I. P. (1972). Resumption of morphine self-administration by ex-addict rats: an attempt to modify tendencies to relapse. Journal of Comparative and Psychological Psychology, 78, 457465.Google Scholar
Kumar, R., Stolerman, I. P., and Steinberg, H. (1970). Psychopharmacology. Annual Review of Psychology, 21, 595628.Google Scholar
Lasagna, L., Von Felsinger, J. M., and Beecher, H. K.(1955). Drug-induced mood changes in man. I. Observations on healthy subjects, chronically ill patients, and ‘postaddicts’. Journal of the American Medical Association, 157, 10061020.Google Scholar
Lint, J. de, and Schmidt, W. (1971). Consumption averages and alcohol prevalence: a brief review of epidemiological investigations. British Journal of Addiction, 66, 97107.Google Scholar
Loh, H. H., Shen, F-H., and Way, E. L. (1969). Inhibition of morphine tolerance and physical dependence development and brain serotonin synthesis by cycloheximide. Biochemical Pharmacology, 18, 27112721.Google Scholar
Madinaveitia, J. (1969). Search for addiction in a new analgesic. In Scientific Basis of Drug Dependence. A Symposium, pp. 155171. Edited by Steinberg, H.. Churchill: London.Google Scholar
Martin, W. R., and Jasinski, D. R. (1969). Physiological parameters of morphine dependence in man—tolerance, early abstinence, protracted abstinence. Journal of Psychiatric Research, 7, 917.CrossRefGoogle ScholarPubMed
Martin, W. R., Wikler, A., Eades, C. G., and Pescor, F. T. (1963). Tolerance to and physical dependence on morphine in rats. Psychopharmacologia, 4, 247260.Google Scholar
Masserman, J. H., and Yum, K. S. (1946). An analysis of the influence of alcohol on experimental neurosis in cats. Psychosomatic Medicine, 8, 3652.Google Scholar
Mello, N. K., and Mendelson, J. H. (1966). Factors affecting alcohol consumption in primates. Psychosomatic Medicine, 28, 529550.Google Scholar
Mitcheson, M., Davidson, J., Hawks, D. V., Hitchens, L., and Malone, S. (1970). Sedative abuse by heroin addicts. Lancet, 1, 606607.Google Scholar
Myers, R. D., and Holman, R. B. (1967). Failure of stress of electric shock to increase ethanol intake in rats. Quarterly Journal of Studies on Alcohol, 28, 132137.Google Scholar
Nichols, J. R. (1965). How opiates change behavior. Scientific American, 212, No. 2, 8088.Google Scholar
Nichols, J. R., Headlee, C. P., and Coppock, H. W. (1956). Drug addiction I. Addiction by escape training. Journal of the American Pharmaceutical Association, 45, 788791.Google Scholar
Nichols, J. R., and Hsiao, S. (1967). Addiction liability of albino rats: breeding for quantitative differences in morphine drinking. Science, 157, 561563.CrossRefGoogle ScholarPubMed
Paton, W. D. M. (1968). Drug dependence—a sociopharmacological assessment. Advancement of Science, 25, 200212.Google Scholar
Routtenberg, A. (1968). The two-arousal hypothesis: reticular formation and limbic system. Psychological Review, 75, 5180.CrossRefGoogle ScholarPubMed
Russell, R. W. (1964). Extrapolation from animals to man: introduction. Animal Behaviour and Drug Action, pp. 410418. Edited by Steinberg, H., de Reuck, A. V. S., and Knight, J.. Churchill: London.Google Scholar
Schofield, M. (1971). The Strange Case of Pot. Penguin: Harmondsworth.Google Scholar
Schuster, C. R., and Woods, J. H. (1968). The conditioned reinforcing effects of stimuli associated with morphine reinforcement. International Journal of the Addictions, 3, 223230.CrossRefGoogle Scholar
Schuster, C. R., and Villarreal, J. E. (1968). The experimental analysis of opioid dependence. In Psychopharmacology. A review of progress 1957–1967, pp. 811828. Edited by Efron, D. H., Cole, J. O., Levine, J., and Wittenborn, J. R.. U.S. Public Health Service Publication No. 1836. U.S. Government Printing Office: Washington.Google Scholar
Schuster, C. R., and Thompson, T. (1969). Self administration of and behavioral dependence on drugs. Annual Review of Pharmacology, 9, 483502.Google Scholar
Schuster, C. R., and Balster, R. (1972). Self-administration of agonists. In Proceedings of Symposium on Agonist and Anlagonist Actions of Narcotic Analgesic Drugs. Edited by Kosterlitz, H. W., Collier, H. O. J., and Villareal, J. E.. Macmillan: London. (In press.)Google Scholar
Seevers, M. H., and Deneau, G. A. (1963). Physiological aspects of tolerance and physical dependence. In Physiological Pharmacology. Vol. 1, pp. 565640. Edited by Root, W. S., and Hofmann, F. G.. Academic Press: New York.Google Scholar
Seevers, M. H., and Deneau, G. A. (1968). A critique of the ‘dual action’ hypothesis of morphine physical dependence. In The Addictive States, pp. 199205. Edited by Wikler, A.. Association for Research in Nervous and Mental Disease, Research Publication, Vol. 46. Williams and Wilkins: Baltimore.Google Scholar
Spear, H. B. (1969). The growth of heroin addiction in the United Kingdom. British Journal of Addiction, 64, 245255.Google Scholar
Spragg, S. D. S. (1940). Morphine addiction in champanzees. Conparative Psychology Monographs, 15, 79132.Google Scholar
Steinberg, H., Kumar, R., Kemp, I., and Bartley, H. (1968). Animal behaviour studies and some possible implications for man. In The Pharmacological and Epidemiological Aspects of Adolescent Drug Dependence, pp. 2940. Edited by Wilson, C. W. M.. Pergamon Press: Oxford.Google Scholar
Stolerman, I. P., and Kumar, R. (1970). Preferences for morphine in rats: validation of an experimental model of dependence. Psychopharmacologia, 17, 137150.Google Scholar
Stolerman, I. P., and Kumar, R. (1972). Regulation of drug and water intake in rats dependent on morphine. Psychopharmacologia, 26, 1928.CrossRefGoogle ScholarPubMed
Stolerman, I. P., Kumar, R., and Steinberg, H. (1971). Development of morphine dependence in rats: lack of effect of previous ingestion of other drugs. Psychopharmacologia, 20, 321336.Google Scholar
Tatum, A. L., Seevers, M. H., and Collins, K. H. (1929). Morphine addiction and its physiological interpretation based on experimental evidence. Journal of Pharmacology and Experimental Therapeutics, 36, 447475.Google Scholar
Teasdale, J. (1972). Drug dependence. In Handbook of Abnormal Psychology. 2nd edition. Edited by Eysenck, H. J.. Pitman: London. (In press.)Google Scholar
Thompson, T., and Schuster, C. R. (1964). Morphine self-administration, food-reinforced, and avoidance behaviors in rhesus monkeys. Psychopharmacologia, 5, 8794.CrossRefGoogle ScholarPubMed
Thompson, T., and Ostlund, W. Jr., (1965). Susceptibility to readdiction as a function of the addiction and withdrawal environments. Journal of Comparative and Physiological Psychology, 60, 388392.Google Scholar
Thompson, T., and Pickens, R. (1969). Drug self-administration and conditioning. In Scientific Basis of Drug Dependence. A Symposium, pp. 177198. Edited by Steinberg, H.. Churchill: London.Google Scholar
Valenstein, E. S., Cox, V. C., and Kakolewski, J. W. (1970). Re-examination of the role of the hypothalamus in motivation. Psychological Review, 77, 1631.Google Scholar
Weeks, J. R., and Collins, R. J. (1964). Factors affecting voluntary morphine intake in self-maintained addicted rats. Psychopharmacologia, 6, 267279.CrossRefGoogle ScholarPubMed
Weeks, J. R., and Collins, R. J. (1968). Patterns of intravenous self-injection by morphine-addicted rats. In The Addictive States, pp. 288298. Edited by Wikler, A.. Association for Research in Nervous and Mental Disease, Research Publications, Vol. 46. Williams and Wilkins: Baltimore.Google Scholar
Wikler, A. (1971). Present status of the concept of drug dependence. Psychological Medicine, 1, 377380.Google Scholar
Wikler, A., and Pescor, F. T. (1967). Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and ‘relapse’ in morphine-addicted rats. Psychopharmacologia, 10, 255284.Google Scholar
Wikler, A., and Pescor, F. T. (1970). Persistence of ‘relapse-tendencies’ of rats previously made physically dependent on morphine. Psychopharmacologia, 16, 375384.CrossRefGoogle ScholarPubMed
Wikler, A., Pescor, F. T., Miller, D., and Norrell, H. (1971). Persistent potency of a secondary (conditioned) reinforcer following withdrawal of morphine from physically dependent rats. Psychopharmacologia, 20, 103117.Google Scholar
Willis, J. H. (1969). The natural history of drug dependence: some comparative observations on United Kingdom and United States subjects. In Scientific Basis of Drug Dependence. A Symposium, pp. 301321. Edited by Steinberg, H.. Churchill: London.Google Scholar
Woods, J. H., and Schuster, C. R. (1968). Reinforcement properties of morphine, cocaine, and SPA as a function of unit dose. International Journal of Addictions, 3, 231237.Google Scholar
Yanagita, T., Deneau, G. A., and Seevers, M. H. (1965). Evaluation of pharmacologic agents in the monkey by long term intravenous self or programmed administration. XXIII International Congress of Physiological Sciences. Lectures and symposia, Tokyo, 1965, pp. 453457. International Congress Series No. 87. Excerpta Medica: Amsterdam.Google Scholar