Abstract
Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including “wet dog shakes” and weight loss, were noted in these subjects, but not in controls given placebo pellets and/or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.
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References
Berger, B. D.: Conditioning of food aversions by injections of of psychoactive drugs. J. comp. physiol. Psychol. 81, 21–26 (1972)
Braun, J. J., Snyder, D. R.: Taste aversions and acute methyl mercury poisoning in rats. Bull. Psychon. Soc. 1, 419–420 (1973)
Cochin, J., Kornetsky, C.: Development and loss of tolerance to morphine in the rat after single and multiple injections. J. Pharmacol. exp. Ther. 145, 1–10 (1964)
Frumkin, K.: Physical dependence in rats after low morphine doses. Life Sci. 15, 455–462 (1974)
Garcia, J., Kimeldorf, D. J., Hunt, E. L.: The use of ionizing radiation as a motivating stimulus. Psychol Rev. 68, 383–385 (1961)
Garcia, J., McGowan, B. K., Green, K. F.: Biological constraints on conditioning. In: Classical conditioning. II. Current research and theory, A. Black and W. F. Prokasy, eds., pp. 3–27. New York: Appleton-Century-Crofts 1972
Gibson, R. D., Tingstand, J. E.: Formulation of a morphine pellet suitable for tolerance-physical dependence development in mice. J. Pharmaceut. Sci. 59, 426–427 (1970)
Goldberg, S. R., Schuster, C. R.: Nalorphine: increased sensitivity of monkeys formerly dependent on morphine. Science 166, 1548–1549 (1969)
Himmelsbach, C. K.: Clinical studies of drug addiction. Physical dependence, withdrawal and recovery. Arch. intern. Med. 69, 766–772 (1942)
Maggiolo, C., Huidobro, F.: Administration of pellets of morphine to mice: abstinence syndrome. Acta physiol. lat.-amer. 11, 70–78 (1961)
Martin, W. R.: Opiate antagonists. Pharmacol. Rev. 19, 464–521 (1967)
Martin, W. R., Sloan, J. W.: The pathophysiology of morphine dependence and its treatment with opiate antagonists. Pharmakopsychiat. Neuro-Psychopharmak. 1, 260–270 (1968)
Martin, W. R., Wikler, A., Eades, C. G., Pescor, F. T.: Tolerance to and physical dependence on morphine in rats. Psychopharmacologia (Berl.) 4, 247–260 (1963)
Nachman, M., Ashe, J. H.: Learned taste aversions in rats as a function of dosage, concentration, and route of administration of LiCl. Physiol. Behav. 10, 73–78 (1973)
Rozin, R., Kalat, J. W.: Specific hungers and poison avoidance as adaptive specializations of learning. Psychol. Rev. 78, 459–486 (1971)
Walter Reed Army Institute of Research. Annual Report, pp. 65–66 (1973)
Wei, E., Tseng, L. F., Loh, H., Way, E. L.: Similarity of morphine abstinence signs to thermo-regulatory behavior. Nature (Lond.) 247, 398–399 (1964)
Wikler, A., Pescor, F. T.: Classical conditioning of a morphine abstinence phenomenon, reinforcement of opiate-drinking behavior and “relapse” in morphine-addicted rats. Psychopharmacologia (Berl.) 10, 255–284 (1967)
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Manning, F.J., Jackson, M.C. Enduring effects of morphine pellets revealed by conditioned taste aversion. Psychopharmacology 51, 279–283 (1977). https://doi.org/10.1007/BF00431636
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DOI: https://doi.org/10.1007/BF00431636