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Psychopharmacology

, Volume 109, Issue 1–2, pp 185–190 | Cite as

Contribution of associative and nonassociative processes to the development of morphine tolerance

  • Stephen T. Tiffany
  • David J. Drobes
  • Antonio Cepeda-Benito
Original Investigations

Abstract

The contribution of associative and nonassociative processes to the development of tolerance to the analgesic effects of morphine in rats was investigated in two experiments. Associative contingencies were manipulated by administering a series of moderately high morphine doses (20 mg/kg) either explicitly paired or explicitly unpaired with a distinctive context. During distinctive context exposures, animals were placed for 60 min in plastic boxes located in a room adjacent to the colony room. The distinctiveness of this environment was enhanced by the presence of white noise and a pine scent. Nonassociative processes were manipulated by administering the morphine at either a very short (6 h) or relatively long (96 h) interdose-interval (IDI). Analgesia was measured on a tail-flick test. At the 96 h IDI, tolerance, as indexed by shifts in dose-response curves, was controlled primarily by associative processes. Associative control over tolerance at the long IDI was evident at an immediate test (experiment 1) and was retained for a 30 day interval (experiment 2). In contrast, tolerance that developed at the 6 h IDI was not influenced by associative contingencies at the immediate test (experiment 1) and showed no retention over a 30 day interval (experiment 2). These data suggest that tolerance that developed at the short IDI was nonassociative. Overall, the results indicate that conditions conducive to the development of non-associative tolerance disrupt the acquisition of associative tolerance. Hypotheses regarding the absence of associative effects at the short IDI are reviewed. Methodological implications of these results for evaluations of associative and nonassociative morphine tolerance are also discussed.

Key words

Tolerance Morphine Classical conditioning Associative Nonassociative Tolerance retention Tail-flick Dose-response curves 

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References

  1. Baker TB, Tiffany ST (1985) Morphine tolerance as habituation. Psychol Rev 92:78–108CrossRefPubMedGoogle Scholar
  2. Batson JD, Best MR (1982) Lithium-mediated disruptions of latent inhibition: overshadowing of the unconditioned stimulus in flavor conditioning. Learn Motiv 13:167–184CrossRefGoogle Scholar
  3. Cepeda-Benito A, Tiffany ST (1992) Effect of number of conditioning trials on the development of associative tolerance to morphine. Psychopharmacology 109:172–176PubMedGoogle Scholar
  4. Cohen J, Cohen P (1975) Applied multiple regression/correlational analysis for the behavioral sciences. Lawrence Erlbaum, Hillside, New JerseyGoogle Scholar
  5. Collier HOJ (1984) Cellular aspects of opioid tolerance and dependence. In: Hughes J, Collier HOJ, Rance MJ, Tyers MB (eds) Opioids past, present and future. Taylor & Francis, London, pp 109–125Google Scholar
  6. Dafters RI, Bach L (1985) Absence of environment-specificity in morphine tolerance acquired in nondistinctive environments: habituation or stimulus overshadowing? Psychopharmacology 87:101–106Google Scholar
  7. Dafters RI, Odber J (1989) Effects of dose, interdose interval and drug-signal parameters on morphine analgesic tolerance: implications for current theories of tolerance. Behav Neurosci 103:1082–1090CrossRefPubMedGoogle Scholar
  8. Dafters RI, Odber J, Miller J (1988) Associative and non-associative tolerance to morphine: support for a dual-process habituation model. Life Sci 42:1897–1906CrossRefPubMedGoogle Scholar
  9. Goldstein DB, Goldstein A (1968) Enzyme expansion theory of drug tolerance and physical dependence. In: Association for research in nervous and mental diseases. Research Publication 46. Williams and Wilkins, Baltimore, pp 265–267Google Scholar
  10. Goudie AJ, Demellweek C (1986) Conditioning factors in drug tolerance. In: Goldberg SR, Stolerman IP (eds) Behavioral analysis of drug dependence. Academic Press, New York, pp 225–285Google Scholar
  11. Hinson RW, Siegel S (1983) Anticipatory hyperexcitability and tolerance to the narcotizing effect of morphine in the rat. Behav Neurosci 97:759–767CrossRefPubMedGoogle Scholar
  12. Johnson SM, Fleming WW (1989) Mechanisms of cellular adaptive sensitivity changes: applications to opioid tolerance and dependence. Pharmacol Rev 41:435–488PubMedGoogle Scholar
  13. Kesner RP, Baker TB (1981) A two-process model of tolerance. In: Martinez J, Jensen JL, Messing RB, Rigter HE, McGaugh JL (eds) Endogenous peptides and learning and memory processes. Academic Press, New York, pp 479–518Google Scholar
  14. Kesner RP, Cook DG (1983) Role of habituation and classical conditioning in the development of morphine tolerance. Behav Neurosci 97:4–12CrossRefPubMedGoogle Scholar
  15. LeBlanc AE, Gibbons RJ, Kalant H (1973) Behavioral augmentation of tolerance to ethanol in the rat. Psychopharmacologia 30:117–122Google Scholar
  16. Mackintosh NJ (1983) Conditioning and associative learning. Oxford University Press, New YorkGoogle Scholar
  17. Martin WR (1968) A homeostatic and redundancy theory of tolerance to and dependence on narcotic analgesics. In: Association for research in nervous and mental diseases, Research Publication 46. Williams and Wilkins, Baltimore, pp 206–223Google Scholar
  18. Poulos CX, Cappell H (1991) Homeostatic theory of drug tolerance: a general model of physiological adaptation. Psychol Rev 98:390–408CrossRefPubMedGoogle Scholar
  19. Schindler CW, Gormezano I, Harvey JA (1983) Effect of morphine on acquisition of the classically conditioned nictitating membrane response of the rabbit. J Pharmacol Exp Ther 227:639–643PubMedGoogle Scholar
  20. Schnur P, Martinez RA (1989) Environmental control of morphine tolerance in the hamster. Anim Learn Behav 17:322–327Google Scholar
  21. Siegel S (1975) Evidence from rats that tolerance is a learned response. J Comp Physiol Psychol 89:323–325Google Scholar
  22. Siegel S (1989) Pharmacological conditioning and drug effects. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana, Clifton, NJ, pp 115–180Google Scholar
  23. Solomon RL (1980) The opponent process theory of acquired motivation: the costs of pleasure and the benefits of pain. Am Psychol 35:691–712CrossRefPubMedGoogle Scholar
  24. Tabakoff B, Melchior CL, Hoffman PL (1982) Commentary on alcohol tolerance. Alcohol Clin Exp Res 6:252–259PubMedGoogle Scholar
  25. Terry WS (1976) The effects of priming US representations in short-term memory on Pavlovian conditioning. J Exp Psychol [Anim Behav] 2:354–370CrossRefGoogle Scholar
  26. Tiffany ST, Baker TB (1981) Morphine tolerance in rats: congruence with a Pavlovian paradigm. J Comp Physiol Psychol 95:747–762PubMedGoogle Scholar
  27. Tiffany ST, Maude-Griffin PM (1988) Tolerance to morphine in the rat: associative and nonassociative effects. Behav Neurosci 102:534–543CrossRefPubMedGoogle Scholar
  28. Tiffany ST, Maude-Griffin PM, Drobes D (1991) The effect of dose interval on the development of associative tolerance to morphine in the rat: a dose response analysis. Behav Neurosci 105:49–61CrossRefPubMedGoogle Scholar
  29. Wagner AR (1978) Expectancies and the priming of STM. In: Hulse SH, Fowler H, Honig KW (eds) Cognitive processes in animal behavior. Erlbaum, Hillsdale, NJ, pp 177–209Google Scholar
  30. Wenger JR, Woods SC (1984) Reply to Tabakoff et al. 1984. Science 244:524Google Scholar
  31. Wenger JR, Tiffany TM, Bombardier C, Nicholls K, Woods SC (1981) Ethanol tolerance in the rat is learned. Science 213:575–577PubMedGoogle Scholar
  32. Wolgin DL (1989) The role of instrumental learning in behavioral tolerance to drugs. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana, Clifton, NJ, pp 17–114Google Scholar
  33. Wolgin DL, Benson HD (1990) Tolerance to morphine “anorexia” is not contingent on experience with food while in the drugged state. Behav Neurosci 104:441–448CrossRefPubMedGoogle Scholar
  34. Wolgin DL, Benson HD (1991) Role of associative and nonassociative mechanisms in tolerance to morphine “anorexia”. Pharmacol Biochem Behav 39:279–286CrossRefPubMedGoogle Scholar
  35. Young AM, Sannerud CA (1989) Tolerance to drug discriminative stimuli. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana, Clifton, NJ, pp 221–278Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Stephen T. Tiffany
    • 1
  • David J. Drobes
    • 1
  • Antonio Cepeda-Benito
    • 1
  1. 1.Department of Psychological SciencesPurdue UniversityWest LafayetteUSA

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