Psychopharmacology

, Volume 62, Issue 3, pp 307–314 | Cite as

Naloxone effects on schedule-controlled behavior in morphine-pelleted rats

  • Alice M. Young
  • Travis Thompson
Original Investigations

Abstract

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3–4 days. Naloxone (0.25–1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7–17 days for 0.25 mg/kg naloxone, 9–22 days for 0.50 mg/kg, and 13–28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25–1.0 mg/kg) did not alter performance by placebo-pelleted rats.

Key words

Morphine pellet Naloxone Schedule-controlled behaviors Precipitated abstinence Rats 

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References

  1. Andrews, H. L., Himmelsbach, C. K.: Relation of the intensity of the morphine abstinence syndrome to dosage. J. Pharmacol. Exp. Ther. 81, 288–293 (1944)Google Scholar
  2. Babbini, M., Gaiardi, M., Bartoletti, M.: Changes in operant behavior as an index of a withdrawal state from morphine in rats. Psychon. Sci. 29, 142–144 (1972)Google Scholar
  3. Babbini, M., Gaiardi, M., Bartoletti, M.: Changes in fixed-interval behavior during chronic morphine treatment and morphine abstinence in rats. Psychopharmacologia (Berlin) 45, 255–259 (1976)Google Scholar
  4. Bläsig, J., Herz, A., Reinhold, K., Zieglgänsberger, S.: Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia (Berlin) 33, 19–38 (1973)Google Scholar
  5. Cicero, T. J., Meyer, E. R.: Morphine pellet implantation in rats: quantitative assessment of tolerance and dependence. J. Pharmacol. Exp. Ther. 184, 404–408 (1973)Google Scholar
  6. Djahanguiri, B., Richelle, M., Fontaine, O.: Behavioral effects of a prolonged treatment with small doses of morphine in cats. Psychopharmacologia (Berlin) 9, 363–372 (1966)Google Scholar
  7. Downs, D. A., Woods, J. H.: Morphine, pentazocine and naloxone effects on responding under a multiple schedule of reinforcement in rhesus monkeys and pigeons. J. Pharmacol. Exp. Ther. 196, 298–306 (1976)Google Scholar
  8. Ford, R. D., Balster, R. L.: Schedule-controlled behavior in the morphine-dependent rat. Pharmacol. Biochem. Behav. 4, 569–573 (1976)Google Scholar
  9. Gellert, V. F., Sparber, S. B.: A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats. J. Pharmacol. Exp. Ther. 201, 44–54 (1977)Google Scholar
  10. Gibson, R. D., Tinstad, J. E.: Formulation of a morphineimplantation pellet suitable for tolerance-physical dependence studies in mice. J. Pharm. Sci. 59, 426–427 (1970)Google Scholar
  11. Goldberg, S. R., Morse, W. H., Goldberg, D. M.: Some behavioral effects of morphine, naloxone and nalorphine in the squirrel monkey and the pigeon. J. Pharmacol. Exp. Ther. 196, 625–636 (1976)Google Scholar
  12. Goldberg, S. R., Schuster, C. R.: Conditioned suppression by a stimulus associated with nalorphine in morphine-dependent monkeys. J. Exp. Anal. Behav. 10, 235–242 (1967)Google Scholar
  13. Goldberg, S. R., Schuster, C. R.: Nalorphine: Increased sensitivity of monkeys formerly dependent on morphine. Science 166, 1548–1549 (1969)Google Scholar
  14. Goldberg, S. R., Schuster, C. R.: Conditioned nalorphine-induced abstinence changes: Persistence in post morphine-dependent monkeys. J. Exp. Anal. Behav. 14, 33–46 (1970)Google Scholar
  15. Goldberg, S. R., Woods, J. H., Schuster, C. R.: Nalorphine-induced changes in morphine self-administration in rhesus monkeys. J. Pharmacol. Exp. Ther. 176, 464–471 (1971)Google Scholar
  16. Heifetz, S. A., McMillan, D. E.: Development of behavioral tolerance to morphine and methadone using the schedule-controlled behavior of the pigeon. Psychopharmacologia (Berlin) 19, 40–52 (1971)Google Scholar
  17. Holtzman, S. G., Villarreal, J. E.: Operant behavior in the morphine-dependent rhesus monkey. J. Pharmacol. Exp. Ther. 184, 528–541 (1973)Google Scholar
  18. Manning, F. J., Jackson, M. C.: Enduring effects of morphine pellets revealed by conditioned taste aversion. Psychopharmacology 51, 279–283 (1977)Google Scholar
  19. McMillan, D. E.: Effects of narcotics and narcotic antagonists on operant behavior. In: Narcotic Antagonists: Advances in Biochemical Psychopharmacology, vol. 8, M. C. Braude, L. S. Harris, E. L. May, J. P. Smith, and J. E. Villarreal, eds., pp. 345–359. New York: Raven Press 1974Google Scholar
  20. McMillan, D. E., Dewey, W. L., Harris, L. S.: Characteristics of tetrahydrocannabinol tolerance. Annals N.Y. Acad. Sci. 191, 83–96 (1971)Google Scholar
  21. 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
  22. Ponicki, E.: A simple technique for auto-shaping lever pressing by the rat within a single session. Psychol. Rec. 24, 119–122 (1974)Google Scholar
  23. Thompson, T., Grabowski, J. G.: Reinforcement schedules and multioperant behavior repetoires. New York: Appleton-Century-Crofts 1972Google Scholar
  24. Way, E. L., Loh, H. H., Shen, F.: Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther. 167, 1–8 (1969)Google Scholar
  25. Wei, E.: Assessment of precipitated abstinence in morphine-dependent rats. Psychopharmacologia (Berlin) 28, 35–44 (1973)Google Scholar
  26. Wei, E., Loh, H. H., Way, E. L.: Quantitative aspects of precipitated abstinence in morphine-dependent rats. J. Pharmacol. Exp. Ther. 184, 398–403 (1973)Google Scholar
  27. Winter, C. A., Flataker, L.: Studies on hepatazone (6-morpholino-4,4-diphenyl-3-hepatanone hydrochloride) in comparison with other analgesic drugs. J. Pharmacol. Exp. Ther. 98, 305–317 (1950)Google Scholar
  28. Young, A. M., Thompson, T.: Effects of naloxone on schedule-controlled behavior in morphine-maintained pigeons. J. Pharmacol. Exp. Ther. 205, 236–245 (1978)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Alice M. Young
    • 1
  • Travis Thompson
    • 1
  1. 1.Department of PsychologyUniversity of MinnesotaMinneapolisUSA

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