, Volume 31, Issue 1, pp 35–48 | Cite as

Some agonistic actions of the morphine antagonist levallorphan on behavior and brain monoamines in the rat

  • Harriett R. Steinert
  • Stephen G. Holtzman
  • Robert E. Jewett
Animal Studies


The effects of levallorphan, a narcotic-antagonist analgesic, were studied on locomotor activity, operant behavior (continuous avoidance schedule), and brain monoamine content in the rat. Levallorphan produced an increase in locomotor activity and in the rate of avoidance responding. Brain norepinephrine was significantly decreased 1 h after 256 mg/kg of levallorphan. Brain dopamine (DA) levels were lowered by 64 and 256 mg/kg of levallorphan. There was no effect on brain serotonin levels. The stimulant effects of levallorphan on operant behavior were blocked by simultaneous administration of naloxone. A clear antagonism of the effects of levallorphan on locomotor activity by naloxone could be demonstrated for low doses of levallorphan but not for doses above 16 mg/kg. Naloxone also failed to prevent the depletion of brain catecholamines produced by levallorphan. Naloxone alone had no consistent effect on either of the behaviors under observation or on brain monoamine content. These findings indicate that levallorphan is a stimulant of behavior in the rat, and that the stimulant action is mediated by at least two mechanisms: one which is blocked by naloxone, and one which is not. Furthermore, it is suggested that the rat should be considered as a possible animal model in which to study the agonistic properties of certain narcotic-antagonist analgesics on behavior.

Key words

Naloxone Levallorphan Narcotic Antagonist Locomotor Activity Operant Behavior 


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  1. Ansell, G. B., Beeson, M. F.: A rapid and sensitive procedure for the combined assay of noradrenaline, dopamine, and serotonin in a single brain sample. Analyt. Biochem. 23, 196–206 (1968).Google Scholar
  2. Archer, S., Harris, L. S., Albertson, N. F., Tullar, B. F., Pierson, A. K.: Narcotic antagonists as analgesics; laboratory aspects. In: Molecular Modification in Drug Design, Advances in Chemistry Series No. 45. R. F. Gould (ed.), pp. 162–169. American Chemical Society 1964.Google Scholar
  3. Blumberg, H., Dayton, H. B., George, M., Rappaport, D. N.: N-allylnoroxymorphone: a potent narcotic antagonist. Fed. Proc. 20, 311 (1961).Google Scholar
  4. Collier, H. O. J., Schneider, C.: Some agonist and antagonist properties of morphine antagonists in rodents. In: Agonist and Antagonist Actions of Narcotic Analgesic Drugs. H. W. Kosterlitz, H. O. J., Collier and J. E. Villarreal, eds., pp. 128–135. Baltimore: University Park Press 1973.Google Scholar
  5. Dews, P. B., Morse, W. H.: Behavioral pharmacology. Ann. Rev. Pharmacol. 1, 145–174 (1961).Google Scholar
  6. Eddy, N. B., Martin, W. R.: Drug dependence of specific opiate antagonist type. Pharmakopsychiat. Neuro-Psychopharmak. 3, 73–82 (1970).Google Scholar
  7. Edwards, A. L.: Experimental Design in Psychological Research. New York: Holt, Rinehart and Winston 1965.Google Scholar
  8. Fraser, H. F., Harris, L. S.: Narcotic and narcotic antagonist analgesics. Ann. Rev. Pharmacol. 7, 277–300 (1967).Google Scholar
  9. Heise, G. A., Boff, E.: Continuous avoidance as a base-line for measuring behavioral effects of drugs. Psychopharmacologia (Berl.) 3, 264–282 (1962).Google Scholar
  10. Holtzman, S. G., Jewett, R. E.: Interactions of morphine and nalorphine with physostigmine on operant behavior in the rat. Psychopharmacologia (Berl.) 22, 384–395 (1971).Google Scholar
  11. Holtzman, S. G., Jewett, R. E.: Some actions of pentazocine on behavior and brain monoamines in the rat. J. Pharmacol. exp. Ther. 181, 346–356 (1972a).Google Scholar
  12. Holtzman, S. G., Jewett, R. E.: Stimulation of behavior in the rat by cyclazocine. Proc. V. Int. Cong. Pharmacol. p. 105 (1972b).Google Scholar
  13. Kelleher, R. T., Morse, W. H.: Determinants of the specificity of behavioral effects of drugs. Ergebn. Physiol. 60, 1–56 (1968).Google Scholar
  14. Martin, W. R.: Opioid Antagonists. Pharmacol. Rev. 19, 463–521 (1967).Google Scholar
  15. McMillan, D. E., Harris, L. S.: Behavioral and morphine-antagonist effects of the optical isomers of pentazocine and cyclazocine. J. Pharmacol. exp. Ther. 180, 269–279 (1972).Google Scholar
  16. McMillan, D. E., Morse, W. H.: Some effects of morphine and morphine antagonists on schedule-controlled behavior. J. Pharmacol. exp. Ther. 157, 175–184 (1967).Google Scholar
  17. McMillan, D. E., Wolf, P. S., Carchman, R. A.: Antagonism of the behavioral effects of morphine and methadone by narcotic antagonists in the pigeon. J. Pharmacol. exp. Ther. 175, 443–458 (1970).Google Scholar
  18. Rethy, C. R., Smith, C. B., Villarreal, J. E.: Effects of narcotic analgesics upon the locomotor activity and brain catecholamine content of the mouse. J. Pharmacol. exp. Ther. 176, 472–479 (1971).Google Scholar
  19. Schneider, C.: Behavioral effects of some morphine antagonists and hallucinogens in the rat. Nature (Lond.) 220, 586–587 (1968).Google Scholar
  20. Sidman, M.: Avoidance conditioning with brief shock and no exteroceptive warning signal. Science 118, 157–158 (1953).Google Scholar
  21. Spector, S., Sjoerdsma, A., Udenfriend, S.: Blockade of endogenous norepinephrine synthesis by α-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965).Google Scholar
  22. Villarreal, J. E.: Recent advances in the pharmacology of morphine-like drugs. In: Advances in Mental Science, Vol. 2: Drug Dependence. R. T. Harris, C. R. Schuster and D. McIsaac, eds., pp. 83–116. Austin: University of Texas Press 1970.Google Scholar
  23. Weiss, B., Laties, V. G.: Behavioral pharmacology. Ann. Rev. Pharmacol. 9, 297–326 (1969).Google Scholar
  24. Wray, S. R., Cowan, A.: The effects of naloxone, chlorpromazine, and haloperidol pretreatment on levallorphan-induced disruption of rats' operant behavior. Psychopharmacologia (Berl.) 22, 261–270 (1971).Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • Harriett R. Steinert
    • 1
  • Stephen G. Holtzman
    • 1
  • Robert E. Jewett
    • 1
  1. 1.Department of PharmacologyEmory UniversityAtlanta

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