Abstract
It has often been observed that periods of abuse of non-narcotic drugs precede the development of dependence on opiates, but this correlation does not necessarily imply that there is a simple causal relationship. We have previously described a procedure for inducing rats to drink solutions of morphine in preference to water; self-administration of the drug in this way seems to be a valid model of dependence. For the first 46 days of the experiment described here, solutions of alcohol, amylobarbitone, chlordiazepoxide, cocaine or dexamphetamine were made available to different groups of rats. Most of these drugs were ingested in substantial doses, had clear effects on behaviour and produced characteristic patterns of drinking over the repeated trials. However, there was no unequivocal evidence of dependence, and indeed the rats learned to reject the solutions of dexamphetamine. Ingestion of these drugs did not affect the eventual development of dependence when solutions of morphine were substituted at a later stage, although the avoidance of dexamphetamine seemed to temporarily transfer to morphine. Further studies using other methods and species are needed before inferences can be made about “escalation” to dependence on opioids in man.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amit, Z., Stern, M. H., Wise, R. A.: Alcohol preference in the laboratory rat induced by hypothalamic stimulation. Psychopharmacologia (Berl.) 17, 367–377 (1970).
Cicero, T. J., Myers, R. D., Black, W. C.: Increase in volitional ethanol consumption following interference with a learned avoidance response. Physiol. Behav. 3, 657–660 (1968).
Cox, B. M., Ginsburg, M., Osman, O. H.: Acute tolerance to narcotic analgesic drugs in rats. Brit. J. Pharmacol. 33, 245–256 (1968).
Crossland, J.: Neurohumoral substances and drug abstinence syndromes. P. 94 in abstracts of 7th Congr. of CINP, Prague 1970.
—, Leonard, B. E.: Barbiturate withdrawal convulsions in the rat. Biochem. Pharmacol. 12 (Suppl.), 103 (1963).
Davis, J. D., Lulenski, G. C., Miller, N. E.: Comparative studies of barbiturate selfadministration. Int. J. Addict. 3, 207–214 (1968).
- Miller, N. E.: Fear and pain: their effect on self-injection of amobarbital sodium by rats. Science 1286–1287 (1963).
Deneau, G., Yanagita, T., Seevers, M. H.: Self-administration of psychoactive substances by the monkey. A measure of psychological dependence. Psychopharmacologia (Berl.) 16, 30–48 (1969).
Essig, C. F.: Addiction to non-barbiturate sedative and tranquilizing drugs. Clin. Pharmacol. Ther. 5, 334–343 (1964).
Garcia, J., Ervin, F. R.: Gustatory-visceral and telereceptor-cutaneous conditioning — adaptation in internal and external milieus. Comm. Behav. Biol., Part A 1, 389–415 (1968).
Geber, B. A.: Non-dependent drug use: some psychological aspects, pp. 375–387. In: Scientific basis of drug dependence. H. Steinberg (Ed.). London: Churchill 1969.
Goldstein, A., Judson, B. A.: Alcohol dependence and opiate dependence: lack of relationship in mice. Science 172, 290–292 (1971).
Harris, R. T., Claghorn, J. L., Schoolar, J. C.: Self-administration of minor tranquilizers as a function of conditioning. Psychopharmacologia (Berl.) 13, 81–88 (1968).
Kleinman, M. K., Schmidt, H., Jr., Stewart, A.: Effect of prior injection upon the subsequent drinking of phenobarbital in the rat. J. comp. physiol. Psychol. 61, 402–405 (1966).
Kumar, R., Steinberg, H., Stolerman, I. P.: Inducing a preference for morphine in rats without premedication. Nature (Lond.) 218, 564–565 (1968).
- - - A study of “escalation” to morphine dependence in rats. Proc. XIX. Int. Congr. of Psychology, London 1969 (in the press).
-, Stolerman, I. P.: Experiments on “escalation” to morphine dependence in rats. Abstracts of 7th Congr. of CINP, Prague 1970.
Lester, D.: Self-selection of alcohol by animals, human variation and the etiology of alcoholism. Quart. J. Stud. Alcohol 27, 395–438 (1966).
Lewis, A.: Cannabis — A review of the international clinical literature. pp. 40–63. In: Cannabis. Report by the advisory committee on drug dependence. Her Majesty's Stationery Office, London 1968.
Loh, H. H., Shen, F., Way, E. L.: Inhibition of morphine tolerance and physical dependence development and brain serotonin synthesis by cycloheximide. Biochem. Pharmacol. 18, 2711–2721 (1969).
Maynert, E. W.: Catecholamine metabolism in the brain and adrenal medulla during addiction to morphine and in the early abstinence period. Res. Publ. Ass. nerv. ment. Dis. 46, 89–95 (1968).
Myers, R. D.: Voluntary alcohol consumption in animals: peripheral and intracerebral factors. Psychosom. Med. 28, 484–497 (1966).
Nichols, J. R.: How opiates change behavior. Sci. Amer. 212, 80–88 (1965).
—, Headlee, C. P., Coppock, H. W.: Drug Addiction I. Addiction by escape training. J. Amer. pharm. Ass. 45, 788–791 (1956).
Paton, W. D. M.: A pharmacological approach to drug dependence and drug tolerance. pp. 31–47. In: Scientific basis of drug dependence. H. Steinberg (Ed.). London: Churchill 1969.
Pickens, R., Harris, W. C.: Self-administration of d-amphetamine by rats. Psychopharmacologia (Berl.) 12, 158–163 (1968).
—, Thompson, T.: Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J. Pharmacol. exp. Ther. 161, 122–129 (1968).
Remmer, H.: Tolerance to barbiturates by increased breakdown. pp. 111–128. In: Scientific basis of drug dependence. H. Steinberg (Ed.). London: Churchill 1969.
Rozin, P.: Central or peripheral mediation of learning with long CS-US intervals in the feeding system. J. comp. physiol. Psychol. 67, 421–429 (1969).
Schmidt, H.: Variations in water ingestion: the response to barbiturates. Horizons in Neuropsychopharmacology, vol. 51, pp. 263–284. W. A. Himwich and J. P. Schade (Eds.). Amsterdam: Elsevier 1965.
Schuster, C. R., Thompson, T.: Self-administration of and behavioral dependence on drugs. Ann. Rev. Pharmacol. 9, 483–502 (1969).
Soulairac, A., Soulairac, M. L.: Effects of amphetamine-like substances and l-dopa on thirst, water intake and diuresis, pp. 819–837. In: Amphetamines and related compounds. E. Costa and S. Garattini (Eds.). New York: Raven 1970.
Spengler, J.: Beeinflussung des Nahrungs- und Trinkverhaltens von Ratten durch getrenntes Futter- und Wasserangebot sowie durch Pharmaka. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 238, 312–319 (1960).
Stolerman, I. P., Kumar, R.: Preferences for morphine in rats: validation of an experimental model of dependence. Psychopharmacologia (Berl.) 17, 137–150 (1970).
Thompson, T., Ostlund, W.: Susceptibility to readdiction as a function of the addiction and withdrawal environments. J. comp. physiol. Psychol. 60, 388–392 (1965).
Veale, W. L., Myers, R. D.: Increased alcohol preference in rats following repeated exposures to alcohol. Psychopharmacologia (Berl.) 15, 361–372 (1969).
Weeks, J. R., Collins, R. J.: Patterns of intravenous self-injection by morphineaddicted rats. Res. Publ. Ass. nerv. ment. Dis. 46, 288–298 (1968).
Wikler, A., Martin, W. R., Pescor, F. T., Eades, C. G.: Factors regulating oral consumption of an opioid (etonitazene) by morphine-addicted rats. Psychopharmacologia (Berl.) 5, 55–76 (1963).
—, Pescor, F. T.: Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and ‘relapse’ in morphine-addicted rats. Psychopharmacologia (Berl.) 10, 255–284 (1967).
Winer, B. J.: Statistical principles in experimental design. London: McGraw-Hill 1962.
Wishart, J.: Growth-rate determinations in nutrition studies with the bacon pig, and their analyses. Biometrika 30, 16–28 (1938).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stolerman, I.P., Kumar, R. & Steinberg, H. Development of morphine dependence in rats: Lack of effect of previous ingestion of other drugs. Psychopharmacologia 20, 321–336 (1971). https://doi.org/10.1007/BF00403564
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00403564