Skip to main content
Log in

A comparison of some pharmacological actions of morphine and Δ9-tetrahydrocannabinol in the mouse

  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The effects of morphine and Δ9-tetrahydrocannabinol (THC) on the tail-flick reflex, body temperature, and catecholamine synthesis were examined in the mouse in order to compare their effects in a single species and strain under uniform conditions. Naloxone antagonism of THC and cross-tolerance between morphine and THC were also studied. Both morphine and THC produced antinociception, hypothermia, and increased catecholamine synthesis at 30 min after s.c. injection. Morphine produced greater increases in dopamine synthesis and was a more potent antinociceptive agent, while THC produced greater increases in norepinephrine synthesis and was a more potent hypothermic agent. Naloxone pretreatment (1 mg/kg) partially antagonized the hypothermia and increase in catecholamine synthesis produced by THC. There was also crosstolerance between morphine and THC, but it was asymmetric in that THC-tolerant animals were crosstolerant to only the hypothermic action of morphine and morphine-tolerant animals cross-tolerant to only the antinociceptive action of THC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bhargava, H. N.: Effect of some cannabinoids on naloxonepercipitated abstinence in morphine dependent mice. Psychopharmacology 49, 267–270 (1976)

    Google Scholar 

  • Bloom, A. S., Dewey, W. L., Harris, L. S., Brosius, K. K.: The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines. J. Pharmacol. Exp. Ther 198, 33–41 (1976a)

    Google Scholar 

  • Bloom, A. S., Johnson, K. M., Bowman, F. J., Dewey, W. L.: Correlation between the effects of several cannabinoids on catecholamine synthesis, body temperature and behavior. Fed. Proc. 35, 310 (1976b)

    Google Scholar 

  • Bloom, A. S., Dewey, W. L., Harris, L. S., Brosius, K. K.: 9-nor-9β-OH-Hexahydrocannabinol a cannabinoid with potent antinociceptive activity: comparisons with morphine. J. Pharmacol. Exp. Ther. 200, 263–270 (1977)

    Google Scholar 

  • Buxbaum, D. M.: Analgesic activity of Δ9-tetrahydrocannabinol in the rat and mouse. Psychopharmacologia (Berl.) 24, 275–280 (1972)

    Google Scholar 

  • Chesher, G. B., Dahl, C. J., Everingham, M., Jackson, D. M., Marchant-Williams, H., Starmer, G. A.: The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice. Br. J. Pharmacol. 49, 588–594 (1973)

    Google Scholar 

  • Cradock, J. C., Davignon, J. P., Litterst, G. L., Guarino, A. M.: An intravenous formulation of Δ9-tetrahydrocannabinol using a non-ionic surfactant. J. Pharm. Pharmacol. 25, 345 (1973)

    Google Scholar 

  • Dewey, W. L., Harris, L. S., Howes, J. F., Kennedy, J. S., Granchelli, F. E., Pars, H. G., Razdan, R. K.: Pharmacology of some marihuana constituents and two hetrocyclic analogues. Nature 266, 1265–1267 (1970b)

    Google Scholar 

  • Dewey, W. L., Harris, L. S., Howes, J. F., Nuite, J. A.: The effect of various neurohumoral modulators on the activity of morphine and the narcotic antagonists in the tail-flick and phenylquione tests. J. Pharmacol. Exp. Ther. 175, 435–442 (1970a)

    Google Scholar 

  • Dewey, W. L., Harris, L. S., Kennedy, J. S.: Some pharmacological and toxicological effects of l-trans-Δ8 and l-trans-Δ9 in laboratory rodents. Arch. Int. Pharmacodyn. Ther. 196, 133–145 (1971)

    Google Scholar 

  • Feldberg, W., Meyers, R. D.: A new concept of temperature regulation by amines in the hypothalamus. Nature 200, 1325 (1963)

    Google Scholar 

  • Gauchy, C., Agid, Y., Glowinski, J., Cheramy, A.: Acute effects of morphine on dopamine synthesis and release and tyrosine metabolism in the rat striatum. Eur. J. Pharmacol. 22, 311–319 (1973)

    Google Scholar 

  • Haavik, C. O.: Marijuana induced hypothermia. In: Drugs and hypothermia symposium. Fed. Proc. (in press, 1977)

  • Haavik, C. O., Hardman, H. F.: Evaluation of the hypothermia action of tetrahydrocannabinols in mice and squirrel monkeys. J. Pharmacol. Exp. Ther. 197, 568–574 (1973)

    Google Scholar 

  • Harris, L. S., Pierson, A. K.: Some narcotic anatagonists in the benzomorphan series. J. Pharmacol. Exp. Ther. 143, 141–148 (1964)

    Google Scholar 

  • Hine, B., Friedman, E., Torrelio, M., Gershon, S.: Morphine dependent rats. Blockade of precipitated abstinence by tetrahydrocannabinol. Science 187, 443–445 (1975)

    Google Scholar 

  • Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose effect experiments. J. Pharmacol. Exp. Ther. 96, 99–113 (1949)

    Google Scholar 

  • Lotti, V. J.: Body temperature responses to morphine central sites and mechanisms of action. In: The pharmacology of thermoregulation, E. Schönbaum and P. Lomax, eds., pp. 382–394. Basel: S. Karger 1973

    Google Scholar 

  • McMillan, D. E., Dewey, W. L., Harris, L. S.: Characteristics of tetrahydrocannabinol tolerance. Ann. N.Y. Acad. Sci. 191, 83–99 (1971)

    Google Scholar 

  • Oka, T., Nozaki, M., Hosoya, E.: Effects of p-chlorophenylalanine and cholinergic antagonists on body temperature changes induced by the administration of morphine to non-tolerant and morphine tolerant rats. J. Pharmacol. Exp. Ther. 180, 136–143 (1972)

    Google Scholar 

  • Sasame, H. A., Perez-Gruet, J., Dichiara, G., Tagliamonte, A., Tagliamonte, P., Gessa, G. L.: Evidence that dopamine blocks receptors in the brain. J. Neurochem. 19, 1953–1957 (1972)

    Google Scholar 

  • Shellenberger, M. K., Gordon, J.: A rapid simplified procedure for simultaneous assay of norepinephrine, dopamine and 5-hydroxytryptamine from discrete brain areas. Anal. Biochem. 39, 356–372 (1971)

    Google Scholar 

  • Singh, P. P., Das, P. K.: Role of catecholamines in the hypothermic activity of cannabis in albino rats. Psychopharmacology 50, 199–204 (1976)

    Google Scholar 

  • Smith, C. B., Sheldon, M. I., Bednarczyk, J. H., Villarreal, J. E.: Morphine induced increases in the incorporation of 14C-tyrosine into 14C-dopamine and 14C-norepinephrine in the mouse brain: antagonism by naloxone and tolerance. J. Pharmacol. Exp. Ther. 180, 547–557 (1972)

    Google Scholar 

  • Walkes, T. B., Udenfriend, S.: Fluorometric method for estimation of tyrosine in plasma and tissues. J. Lab. Clin. Med. 50, 733–736 (1957)

    Google Scholar 

  • Weiner, N., Rabadjiji, M.: The effect of nerve stimulation on the synthesis and metabolism of norepinephrine in the isolated guinea pig hypogastric nerve-vas deferens preparation. J. Pharmacol. Exp. Ther. 160, 61–71 (1968)

    Google Scholar 

  • Wilson, R. S., May, E. L.: Analgesic properties of the tetrahydrocannabinols, their metabolites and analogs. J. Med. Chem. 18, 700–703 (1975)

    Google Scholar 

  • Winer, B.: Statistical principles in experimental design. New York: McGraw-Hill 1972

    Google Scholar 

  • Zigmond, M. J., Wurtman, R. J.: Daily rhythm in the accumulation of brain catecholamines synthesized from circulating 3H-tyrosine. J. Pharmacol. Exp. Ther. 172, 416–422 (1970)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bloom, A.S., Dewey, W.L. A comparison of some pharmacological actions of morphine and Δ9-tetrahydrocannabinol in the mouse. Psychopharmacology 57, 243–248 (1978). https://doi.org/10.1007/BF00426745

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00426745

Key words

Navigation