Skip to main content
Log in

Asymmetrical cross-tolerance between morphine and scopolamine induced antinociception in the primate: Differential sites of action

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Two experiments explored the role of the cholinergic system in mediating morphine induced analgesia in the rhesus monkey. Experiment 1 tested for cross-tolerance between two antinociceptive compounds, morphine and scopolamine, using the shock titration technique. Tolerance to morphine attenuated the response to scopolamine but tolerance to scopolamine had no effect on morphine induced antinociception. In Experiment 2, the shock threshold was not modified by injections of scopolamine or arecoline into brain sites which had previously been found to be responsive (in terms of antinociception) to morphine injections. These findings are interpreted to imply that morphine and scopolamine do not exert their antinociceptive effects through identical neural substrates, although Experiment 1 does suggest a certain degree of overlap between such substrates.

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

  • Albe-Fessard, D., Besson, J. M.: Convergent thalamic and cortical projections—the non-specific system. In: Handbook of sensory physiology: somatosensory system, Vol. 2, A.Iggo, ed., pp. 489–560. Berlin-Heidelberg-New York: 1966.

  • Beleslin, D., Polak, R. L.: Depression by morphine and chloralose of acetylcholine release from the cat's brain. J. Physiol. (Lond.) 177, 411–419 (1965)

    Google Scholar 

  • Bhargava, U. N., Way, E. L.: Acetylcholinesterase inhibition and morphine effects in morphine tolerant and dependent mice. J. Pharmacol. exp. Ther. 183, 31–40 (1972)

    Google Scholar 

  • Bradley, P. B., Key, B. J.: A comparative study of the effects of drugs on the arousal system of the brain. Brit. J. Pharmacol. 14, 340–349 (1959)

    Google Scholar 

  • Bradley, P. B., Wolstencroft, J. H.: Effects of acetylcholine, nicotine, and muscarine on brainstem neurons. Ann. N. Y. Acad. Sci. 142, 15–20 (1967)

    Google Scholar 

  • de Jongh, D. K.: Remarks on the mechanism of analgesic action of morphine. Acta physiol. Pharmacol. neer. 3, 164–172 (1954)

    Google Scholar 

  • Denisenko, D. P.: Pharmacological blocking of central cholinoreactive systems and the possibilities of its therapeutic application. In: Pharmacology of cholinergic and adrenergic transmission. G. B. Koelle, W. W. Douglas, A. Carlson, and V. Trcka, eds. New York: MacMillan 1965

    Google Scholar 

  • Harris, L. S.: Central neurohumoral systems involved with narcotic agonists and antagonists. Fed. Proc. 29, 28–32 (1970)

    Google Scholar 

  • Harris, L. S., Dewey, W. L., Howes, J. F., Kennedy, J. S., Pars, H.: Narcotic-antagonist analgesics: interactions with cholinergic systems. J. Pharmacol. exp. Ther. 169, 17–22 (1969)

    Google Scholar 

  • Hug, C. C.: Characteristics and theories related to acute and chronic tolerance development. In: Chemical and biological aspects of drug Dependence. S. J. Mulé and H. Brill, eds., pp. 307–358. Cleveland: CRC Press 1972

    Google Scholar 

  • Ireson, J. D.: A comparison of the antinociceptive actions of cholinomimetic and morphine-like drugs. Brit. J. Pharmacol. 40, 92–101 (1970)

    Google Scholar 

  • Jhamandas, K., Phillis, J. W., Pinsky, C.: Effects of narcotic analgesics and antagonists on the in vivo release of acetylcholine from the cerebral cortex of the cat. Brit. J. Pharmacol. 43, 53–66 (1971)

    Google Scholar 

  • Killam, E. K.: Pharmacology of the reticular formation. In: Psycho-Pharmacology. A review of progress. D. H. Efron et al., eds. PHS Publication No. 1836. Washington, D. C.: US Government Printing Office 1968

    Google Scholar 

  • Krug, M., Schmidt, J., Matthies, H.: Beeinflussung des Impulsmusters von spontan tÄtigen Neuronen der Pontine formatio reticularis der Ratte durch Noradrenalin, Serotonin und Azetylcholin. Acta biol. med. germ. 25, 455–467

  • Krupp, P., Monnier, M.: The unspecific intralaminary modulating system of the thalamus. In: International review of neurobiology. C. C. Pfeiffer and J. R. Smythies, eds., Vol. 9. New York: Academic Press 1966

    Google Scholar 

  • Little, J. J., Rees, J. M. H.: Tolerance development to the antinociceptive actions of morphine, amphetamine, physostigmine and 2-aminoindane in the mouse. Experientia (Basel) 30, 930–932 (1974)

    Google Scholar 

  • Martin, W. R.: Pharmacological redundancy as an adaptive mechanism in the central nervous system. Fed. Proc. 29, 13–18 (1970)

    Google Scholar 

  • Metys, J., Wagner, N., Metysova, J., Herz, A.: Studies on the central antinociceptive action of cholinomimetic agents. Int. J. Neuropharmacol. 8, 413–425 (1969)

    Google Scholar 

  • Nauta, W. J. H.: Hippocampal projections and related neural pathways to the midbrain in the cat. Brain 81, 319–340 (1958)

    Google Scholar 

  • Paton, W. D. M.: The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Brit. J. Pharmacol. 12, 119–127 (1957)

    Google Scholar 

  • Pert, A.: The cholinergic system and nociception in the primate: Interactions with morphine. Psychopharmacologia (Berl.) 44, 131–137 (1975)

    Google Scholar 

  • Pert, A., Yaksh, T.: Sites of morphine induced analgesia in the primate brain: relation to pain pathways. Brain Res. 80, 135–140 (1974)

    Google Scholar 

  • Pleuvry, B. J.: Cross-tolerance between methylamphetamine and morphine in the mouse. J. Pharmacol. 23, 969–970 (1971)

    Google Scholar 

  • Pleuvry, B. J., Tobias, M. A.: Comparison of the antinociceptive activities of physostigmine, oxotremorine and morphine in the mouse. Brit. J. Pharmacol. 43, 706–714 (1971)

    Google Scholar 

  • Seevers, M. H., Deneau, G. A.: Physiological aspects of tolerance and physical dependence. In: Physiological pharmacology. W. S. Roat and F. G. Hofmann, eds., pp. 565 to 640. New York: Academic Press 1963

    Google Scholar 

  • Schaumann, N.: Inhibition by morphine of the release of acetylcholine from the intestine of the guinea-pig. Brit. J. Pharmacol. 12, 115–118 (1957)

    Google Scholar 

  • Shute, C. C. D., Lewis, P. R.: Cholinesterase-containing pathways of the hindbrain: afferent cerebellar and centrifugal cochlear fibres. Nature (Lond.) 205, 242–246 (1965)

    Google Scholar 

  • Weiss, B., Laties, V. G.: The psychophysics of pain and analgesia in animals. In: Animal psychophysics. The design and conduct of sensory experiments, W. C. Stebbins, ed., pp. 185–210. New York: Appleton-Century-Crofts 1970

    Google Scholar 

  • Yarbrough, G. G.: Actions of acetylcholine and atropine on cerebral cortical neurons in chronically morphine-treated rats. Life Sci. 15, 1523–1529 (1974)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

In conducting the research described in this report, the investigators adhered to the “Guide for the Care and Use of Laboratory Animals” as promulgated by the Committee on Revision of the Guide for Laboratory Animals Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pert, A., Maxey, G. Asymmetrical cross-tolerance between morphine and scopolamine induced antinociception in the primate: Differential sites of action. Psychopharmacologia 44, 139–145 (1975). https://doi.org/10.1007/BF00421000

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00421000

Key words

Navigation