Abstract
Morphine and saline served as discriminative Stimuli for one group of rats in a 2-lever discrimination task. δ 9-THC and vehicle were discriminative stimuli for a second group. Depression of one lever resulted in reinforcement following the administration of morphine or δ 9-THC and the opposite lever was reinforced after vehicle. A high degree of discriminated responding occurred with both drugs. During daily supplemental injections of morphine or δ 9-THC up to several times the training dose for a period of 2 months, subjects still discriminated morphine or δ 9-THC from vehicle. However, the degree of discrimination was reduced indicating a limited tolerance to either drug. Naloxone precipitated narcoticlike withdrawal symptoms in rats chronically treated with either morphine or δ 9-THC, indicating that there is an interaction between chronic administration of δ 9-THC and the narcotic antagonist, naloxone.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barry, H., Kubena, R. K.: Repeated high doses of δ 9-tetrahydrocannabinol enhanced acquisition of shock avoidance by rats. Proc. Amer. Psychol. Ass. 6, 747–748 (1971)
Bueno, O. F. A., Carlini, E. A.: Dissociation of learning in marihuana tolerant rats. Psychopharmacologia (Berl.) 25, 49–56 (1972)
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)
Cradock, J. C., Davignon, J. P., Litterst, C. L., Guarino, A. M.: An intravenous formulation of δ 9-tetrahydrocannabinol using a non-ionic surfactant. J. Pharm. Pharmacol. 25, 345 (1973)
Deneau, G. A., Kaymakcalan, S.: Physiological and psychological dependence to synthetic δ 9-tetrahydrocannabinol (THC) in rhesus monkeys. Pharmacologist 13, 308 (1971)
Ferraro, D. P., Grilly, D. M.: Lack of tolerance to δ 9-tetrahydrocannabinol in chimpanzees. Science 179, 490–492 (1973)
Gebhart, G. E., Sherman, A. P., Mitchell, C. L.: The influence of stress on tolerance development to morphine in rats tested on the hot plate. Arch. int. Pharmacodyn. 197, 328–337 (1972)
Goldstein, A., Aronow, L., Kalman, S. M.: Principles of drug action. New York: Hoeber 1969
Goodman, L. S., Gilman, A.: The pharmacological basis of therapeutics. New York: MacMillan 1970
Hirschhorn, I. D., Winter, J. C.: Mescaline and lyseric acid diethylamide (LSD) as discriminative stimuli. Psychopharmacologia (Berl.) 22, 64–71 (1971)
Hirschhorn, I. D., Rosecrans, J. A.: Nicotine as a discriminative stimulus: the time course of the cue and the effect of receptor blockers. Pharmacologist 15, 452 (1973)
Hill, H. E., Jones, B. E., Bell, E. L.: State-dependent control of discrimination by morphine and pentobarbitol. Psychopharmacologia (Berl.) 22, 305–313 (1971)
Hollister, L. E., Tinklenberg, J. R.: Subchronic oral doses of marijuana extract. Psychopharmacologia (Berl.) 29, 247–252 (1973)
Kamaei, C., Shimomura, K., Veki, S.: Significance of withdrawal jumping response in predicting physical dependence in mice. Japan J. Pharmacol. 23, 421–426 (1973)
Kubena, R. K., Barry, H.: Generalization of alcohol and atropine stimulus characteristics to other drugs. Psychopharmacologia (Berl.) 15, 196–206 (1969)
Kubena, R. K., Barry, H.: Stimulus characteristics of marijuana components. Nature (Lond.) 235, 397–398 (1972)
Martin, W. R., Fraser, H. F.: A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts. J. Pharmacol. exp. Ther. 133, 388–399 (1961)
McGuigan, G. J.: Experimental psychology, a methodological approach. Englewood Cliffs: Prentice-Hall 1968
McMillan, D. E., Harris, L. S., Frankenheim, J. M., Kennedy, J. S.: 1-δ 9-trans-tetrahydrocannabinol in pigeons: tolerance to the behavioral effects. Science 169, 501–503 (1970)
Overton, D. A.: Dissociated learning in drug states (state dependent learning). In: Psychopharmacology, A review of progress, 1957–1967, pp. 918–930. D. H. Efron, Ed. Washington: U. S. Government Printing Office 1968
Overton, D. A.: Discriminative control of behavior by drug states. In: stimulus properties of drugs, T. Thompson, R. Pickens, Ed. New York: Appleton-Century-Crofts 1971
Rosecrans, J. A., Goodloe, M. H., Bennett, G. J., Hirschhorn, I. D.: Morphine as a discriminative cue: effects of amine depletors and naloxone. Europ. J. Pharmacol. 21, 252–256 (1973)
Williams, E. G., Himmelsbach, C. K., Wikler, A., Ruble, D. C., Lloyd, B. J.: Studies on marijuana and pyrahexyl compound. Publ. Hlth Rep. (Wash.) 61, 1059–1083 (1946)
Way, E. L., Loh, H. H., Shen, F. H.: Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. exp. Ther. 167, 1–8 (1969)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hirschhorn, I.D., Rosecrans, J.A. Morphine and δ9-tetrahydrocannabinol: Tolerance to the stimulus effects. Psychopharmacologia 36, 243–253 (1974). https://doi.org/10.1007/BF00421806
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00421806