, Volume 85, Issue 3, pp 377–382 | Cite as

Effects of morphine, naltrexone, and dextrorphan in untreated and morphine-treated pigeons

  • Charles P. France
  • James H. Woods
Original Investigations


Six pigeons, trained to peck a response key on a fixed-ratio 20 schedule of food reinforcement, were used to examine the effects of morphine, naltrexone, and dextrorphan, before, during, and after chronic treatment with increasing doses of morphine (10.0–100.0 mg/kg/day). Tolerance developed to the rate-decreasing effect of the daily maintenance doses of morphine within 2 days of each dose increase. A small amount of tolerance to morphine and supersensitivity to naltrexone was evident within the 1st week of morphine treatment (10.0 mg/kg/day). Continued administration of morphine (32.0–100.0 mg/kg/day) produced further tolerance to morphine and supersensitivity to naltrexone, as evidenced by a 5-fold increase in the dose of morphine, and 1,000-fold decrease in the dose of naltrexone, necessary to suppress responding. By the 4th week of treatment (100.0 mg/kg/day), a modest tolerance had also developed to the rate-decreasing effects of dextrorphan. Suppression of responding by naltrexone, but not morphine or dextrorphan, was accompanied by a loss in body weight over the 1-to 2-h session in morphine-maintained pigeons; both weight loss and reduced response rates also occurred on termination of morphine treatment. Sensitivity to the rate-decreasing effects of morphine and naltrexone was near normal within 10 days following termination of morphine treatment. The dramatic changes in sensitivity to naltrexone and morphine produced by daily morphine injections, as well as the ability to generate complete dose-effect curves within a single session, indicate that this behavioral preparation may provide sensitive concurrent measures of narcotic tolerance and supersensitivity to antagonists in the pigeon.

Key words

Morphine Naltrexone Dextrorphan Tolerance Supersensitivity Pigeons Operant behavior Fixed ratio schedule 


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  1. Blasig J, Herz A, Reinhold K, Zieglgansberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawall syndrome in rats. Psychopharmacology 33:19–38Google Scholar
  2. Ferster CB, Skinner BF (1957) Schedules of reinforcement. Appleton-Century-Crofts, New YorkGoogle Scholar
  3. Gellert VF, Holtzman SG (1978) Development and mainternance of morphine tolerance and dependence in the rat by scheduled access to morphine drinking solutions. J Pharmacol Exp Ther 205:536–546Google Scholar
  4. Gellert VF, Holtzman SG (1979) Discriminative stimulus effects of naltrexone in the morphine-dependent rat. J Pharmacol Exp Ther 211:596–605Google Scholar
  5. Gellert VF, Morse WH, Goldberg DM (1981) Acute and chronic effects of naltrexone and naloxone on schedule-controlled behavior of squirrel monkeys and pigeons. J Pharmacol Exp Ther 216:500–509Google Scholar
  6. Heifetz SA, McMillan DE (1971) Development of behavioral tolerance to morphine and methadone using the schedule-controlled behavior of the pigeon. Psychopharmacology 19:40–52Google Scholar
  7. Herling S, Coale EH Jr, Valentino RJ, Hein DW, Woods JH (1980) Narcotic discrimination in pigeons. J Pharmacol Exp Ther 214:139–146Google Scholar
  8. Herling S, Solomon RE, Woods JH (1983) Discriminative stimulus effects of dextrorphan in pigeons. J Pharmacol Exp Ther 227:723–731Google Scholar
  9. Hirschhorn ID, Rosecrans JA (1974) Morphine and delta-9-tetrahydrocannabinol: tolerance to the stimulus effects. Psychopharmacology 36:243–253Google Scholar
  10. Jarbe TUC (1978) Discriminative effects of morphine in the pigeon. Pharmacol Biochem Behav 9:411–416Google Scholar
  11. McMillan DE (1974) Effects of narcotics and narcotic antagonists on operant behavior. In: Braude MC, Harris LS, May EL, Smith JP, Villarreal JE (eds) Narcotic Antagonists, vol 8. Adv Biochem Pharmacol, Raven Press, New York, pp 345–359Google Scholar
  12. McMillan DE, Morse WH (1967) Some effects of morphine and morphine antagonists on schedule-controlled behavior. J Pharmacol Exp Ther 157:175–184Google Scholar
  13. McMillan DE, Dewey WL, Harris LS (1971) Characteristics of tetrahydrocannabinol tolerance. Ann NY Acad Sci 191:83–96Google Scholar
  14. Meyer DR, Sparber SB (1977) Evidence of possible opiate dependence during the behavioral depressant action of a single dose of morphine. Life Sci 21:1087–1094Google Scholar
  15. Pert CB, Snyder SH (1976) Opiate receptor binding-enhancement by opiate administration in vivo. Biochem Pharmacol 25:847–853Google Scholar
  16. Spealman RD, Kelleher RT, Morse WH, Goldberg SR (1981) Supersensitivity to the behavioral effects of opiate antagonists. Psychopharmacol Bull 17:54–56Google Scholar
  17. Tang AH, Collins RJ (1978) Enhanced analgesic effects of morphine after chronic administration of naloxone in the rat. Eur J Pharmacol 47:473–474Google Scholar
  18. Valentino RJ, Herling S, Woods JH (1980) Discriminative stimulus effects of naltrexone in narcotic-naive and narcoticpretreated pigeons. Pharmacol Biochem Behav 13:313Google Scholar
  19. Valentino RJ, Herling S, Woods JH (1983) Discriminative stimulus effects of naltrexone in narcotic-naive and morphine-treated pigeons. J Pharmacol Exp Ther 224:307–313Google Scholar
  20. Villarreal JE, Karbowski MG (1974) The actions of narcotic antagonists in morphine-dependent rhesus monkeys. In: Braude MC, Harris LS, May EL, Smith JP, Villarreal JE (eds), Narcotic antagonists, vol 8. Adv Biochem Pharmacol, Raven Press, New York, pp 273–289Google Scholar
  21. Witkin JM, Dykstra LA, Carter RB (1982) Acute tolerance to the discriminative stimulus properties of morphine. Pharmacol Biochem Behav 17:223–228Google Scholar
  22. Woods JH, Carney J (1978) Narcotic tolerance and operant behavior. In: Behavioral tolerance: Research and treatment implications. NIDA Research Monograph 18, US Government Printing Office, Washington DC, pp 54–66Google Scholar
  23. Young AM, Thompson T (1978) Effects of naloxone on schedule-controlled behavior in morphine-maintained pigeons. J Pharmacol Exp Ther 205:236–245Google Scholar
  24. Zukin RS, Sugarman JR, Fitz-Syage ML, Gardner EL, Zukin SR, Gintzler AR (1982) Naltrexone-induced opiate receptor supersensitivity. Brain Res 245:285–292Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Charles P. France
    • 1
  • James H. Woods
    • 1
  1. 1.Departments of Psychology and PharmacologyUniversity of Michigan, Medical SchoolAnn ArborUSA

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