Abstract
The acquisition of associative tolerance to the analgesic effects of morphine as assessed on the hotplate test was investigated in two experiments. Associative contingencies were manipulated by giving rats eight moderately high morphine doses (20 mg/kg) either paired or unpaired with a distinctive context at a 96-h interdose interval. Tolerance was evaluated as shifts in dose-response curves of morphine-experienced relative to morphine-naive animals tested in the distinctive context. Experiment 1, in which independent groups of animals were tested with hot-plate temperatures of 50°C (N = 302) and 54°C (N = 175), produced no evidence of context-specific tolerance to morphine. Experiment 2 (N = 200) evaluated the effect of contextual contingencies of drug delivery on the development of morphine tolerance in animals tested on either the hot-plate or the tailflick test. As found in Experiment 1, animals tested on the hot plate showed no context-specific tolerance, whereas animals tested on the tailflick displayed pronounced associative-tolerance effects. The data suggest that the hot plate, as opposed to other tests of analgesia, does not provide a sensitive measure of associative morphine tolerance.
Article PDF
Similar content being viewed by others
References
Adams, W. J., Yeh, S. Y., Woods, L. A., & Mitchell, C. L. (1969). Drug-test interaction as a factor in the development of tolerance to the analgesic effect of morphine. Journal of Pharmacology & Experimental Therapeutics, 168, 251–257.
Baker, T. B., & Tiffany, S. T. (1985). Morphine tolerance as habituation. Psychological Review, 92, 78–108.
Bardo, M. T., & Hughes, R. W. (1979). Exposure to a nonfunctional hotplate as a factor in the assessment of morphine-induced analgesia and analgesic tolerance in rats. Pharmacology, Biochemistry & Behavior, 10, 481–485.
Carter, B. L., & Tiffany, S. T. (1996). Cross-tolerance of associative and nonassociative morphine tolerance in the rat with mu- and kappa-specific opioids. Psychopharmacology, 123, 289–296.
Cepeda-Benito, A., & Tiffany, S. T. (1992). Effect of the number of conditioning sessions on the development of associative tolerance to morphine. Psychopharmacology, 109, 172–176.
Cepeda-Benito, A., & Tiffany, S. T. (1995). Role of drug-administration cues in the associative control of morphine tolerance in the rat. Psychopharmacology, 122, 312–316.
Cepeda-Benito, A., & Tiffany, S. T. (in press). Unsignaled morphine delivery does not disrupt the development of associative morphine tolerance in the rat. Pharmacology, Biochemistry & Behavior.
Chen, C. S. (1968). A study of the alcohol-tolerance effect and an introduction of a new behavioral technique. Psychopharmacologia, 12, 443–440.
Cohen, J., & Cohen, P. (1975). Applied multiple regression/correlational analysis for the behavioral sciences. Hillsdale, NJ: Erlbaum.
Cox, L. S., & Tiffany, S. T. (in press). Associative and nonassociative tolerance to morphine in the rat: Effects of dose and interdose interval. Pharmacology, Biochemistry & Behavior.
Dafters, R., & Bach, L. (1985). Absence of environment-specificity in morphine tolerance acquired in nondistinctive environments: Habituation or stimulus overshadowing? Psychopharmacology, 87, 101–106.
Dafters, R., & Odber, J. (1989). Effects of dose, interdose interval, and drug-signal parameters on morphine analgesic tolerance: Implications for current theories of tolerance. Behavioral Neuroscience, 103, 1082–1090.
Dafters, R. I., Odber, J., & Miller, J. (1988). Associative and non-associative tolerance to morphine: Support for a dual-process habituation model. Life Sciences, 42, 1897–1906.
Goudie, A. J., & Demellweek, C. (1986). Conditioning factors in drug tolerance. In S. R. Goldberg & I. P. Stolerman (Eds.), Behavioral analysis of drug dependence (pp. 225–285). New York: Academic Press.
Hayes, R. L., & Mayer, D. J. (1978). Morphine tolerance: Is there evidence for a conditioning model? Science, 200, 343–344.
Jensen, T. S., & Yaksh, T. L. (1986). Comparison of antinociceptive action of morphine in the periaqueductal gray, medial and paramedial medulla in rat. Brain Research, 363, 99–113.
Jóhannesson, T., & Woods, L. A. (1964). Analgesic action and brain and plasma levels of morphine and codeine in morphine tolerant, codeine tolerant and non-tolerant rats. Acta Pharmacologica et Toxicologica, 21, 381–396.
Kalant, H., LeBlanc, A. E., & Gibbins, R. J. (1971). Tolerance to, and dependence on, some nonopiate psychotropic drugs. Pharmacological Reviews, 23, 135–191.
Krank, M. D. (1987). Conditioned hyperalgesia depends on the pain sensitivity measure. Behavioral Neuroscience, 101, 854–857.
Krank, M. D., Hinson, R. E., & Siegel, S. (1981). Conditioned hyperalgesia is elicited by environmental signals of morphine. Behavioral & Neural Biology, 32, 148–157.
O’Callaghan, J. P., & Holtzman, S. G. (1975). Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure. Journal of Pharmacology & Experimental Therapeutics, 192, 497–505.
Poulos, C. X., & Cappell, H. (1991). Homeostatic theory of drug tolerance: A general model of physiological adaptation. Psychological Review, 98, 390–408.
Rochford, J., & Stewart, J. (1987). Morphine attenuation of conditioned autoanalgesia: Implications for theories of situation-specific tolerance to morphine analgesia. Behavioral Neuroscience, 101, 690–700.
Schuster, C. R., Dockens, W. S., & Woods, J. H. (1966). Behavioral variables affecting the development of amphetamine tolerance. Psychopharmacologia, 9, 170–182.
Sherman, J. E. (1979). The effects of conditioning and novelty on the rats’ analgesic and pyretic responses to morphine. Learning & Motivation, 10, 381–418.
Sherman, J. E., Proctor, C., & Strub, H. (1982). Prior hotplate exposure enhances morphine analgesia in tolerant and drug-naive rats. Pharmacology, Biochemistry & Behavior, 17, 229–232.
Siegel, S. (1975). Evidence from rats that morphine tolerance is a learned response. Journal of Comparative & Physiological Psychology, 89, 498–506.
Siegel, S. (1976). Morphine analgesic tolerance: Its situation specificity supports a Pavlovian conditioning model. Science, 193, 323–325.
Siegel, S. (1977). Morphine tolerance acquisition as an associative process. Journal of Experimental Psychology: Animal Behavior Processes, 3, 1–13.
Siegel, S., Hinson, R. E., & Krank, M. D. (1978). The role of predrug signals in morphine analgesic tolerance: Support for a Pavlovian conditioning model of tolerance. Journal of Experimental Psychology: Animal Behavior Processes, 4, 188–196.
Siegel, S., Hinson, R. E., & Krank, M. D. (1981). Morphine-induced attenuation of morphine tolerance. Science, 212, 1533–1534.
Sinclair, J. G., Main, C. D., & Lo, G. F. (1988). Spinal vs. supraspinal actions of morphine on the rat tail-flick reflex. Pain, 33, 357–362.
Sribanditmongkol, P., Sheu, M. J., & Tejwani, G. A. (1994). Inhibition of morphine tolerance and dependence by diazepam and its relation to the CNS met-enkephalin levels. Brain Research, 645, 1–12.
Tiffany, S. T., & Baker, T. B. (1981). Morphine tolerance in rats: Congruence with a Pavlovian paradigm. Journal of Comparative & Physiological Psychology, 95, 747–762.
Tiffany, S. T., & Baker, T. B. (1986). Tolerance to alcohol: Psychological models and their application to alcoholism. Annals of Behavioral Medicine, 8, 7–12.
Tiffany, S. T., & Cepeda-Benito, A. (1994). An examination of conditioned tolerance and potential compensatory responses on four assays of morphine analgesia. In Problems of drug dependence 1993 (National Institute on Drug Abuse Research Monograph No. 140, U.S. Department of Health and Human Services). Washington, DC: U.S. Government Printing Office.
Tiffany, S. T., Drobes, D. J., & Cepeda-Benito, A. (1992). Contribution of associative and nonassociative processes to the development of morphine tolerance. Psychopharmacology, 109, 185–190.
Tiffany, S. T., & Maude-Griffin, P. M. (1988). Tolerance to morphine in the rat: Associative and nonassociative effects. Behavioral Neuroscience, 102, 534–543.
Tiffany, S. T., Maude-Griffin, P. M., & Drobes, D. J. (1991). The effect of interdose interval on the development of associative and nonassociative tolerance. Behavioral Neuroscience, 105, 49–61.
Tiffany, S. T., Petrie, E. C., Baker, T. B., & Dahl, J. (1983). Conditioned morphine tolerance in the rat: Absence of a compensatory response and cross-tolerance with stress. Behavioral Neuroscience, 97, 335–353.
Walter, T. A., & Riccio, D. C. (1983). Overshadowing effects in the stimulus control of morphine analgesic tolerance. Behavioral Neuroscience, 97, 658–662.
Westbrook, R. F., & Greeley, J. D. (1992). Conditioned tolerance to morphine hypoalgesia: Compensatory hyperalgesia in the experimental group or conditioned hypoalgesia in the control group? Quarterly Journal of Experimental Psychology, 45B, 161–187.
Wolgin, D. L. (1989). The role of instrumental learning in behavioral tolerance to drugs. In A. J. Goudie & M. W. Emmit-Oglesby (Eds.), Psychoactive drugs: Tolerance and sensitization (pp. 17–114). Clifton, NJ: Humana Press.
Young, A. M., & Goudie, A. J. (1995). Adaptive processes regulating tolerance to behavioral effects of drugs. In F. E. Bloom, D. J. Kupfer, B. S. Bunney, R. D. Ciaranello, K. L. Davis, G. F. Koob, et al. (Eds.), Psychopharmacology: The fourth generation of progress (pp. 657–811). New York: Raven Press.
Author information
Authors and Affiliations
Corresponding author
Additional information
This research was supported by Research Grant R01 DA04050 from the National Institute on Drug Abuse awarded to S.T.T.
We thank Peggy Treece for her help in manuscript preparation.
Rights and permissions
About this article
Cite this article
Cepeda-Benito, A., Tiffany, S.T. Test-specific manifestations of associative tolerance to the analgesic effects of morphine in the rat. Psychobiology 24, 327–332 (1996). https://doi.org/10.3758/BF03327052
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3758/BF03327052