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Reversibility of morphine tolerance and dependence in guinea pig brain and myenteric plexus

Abstract

WHEN guinea pigs are exposed continuously to high morphine concentrations, tolerance and physical dependence develop within a few days in both the central nervous system (CNS) and the myenteric plexus. In the plexus morphine tolerance is associated with subsensitivity to the inhibitory catecholamines and supersensitivity to the excitatory neuro-transmitter serotonin (5-hydroxytryptamine, 5-HT)1,2. We have investigated the following questions about these phenomena, (a) After opiate withdrawal in animals made tolerant and dependent, would the altered sensitivities to neurotransmitters in the plexus return to normal? (b) If so, would loss of tolerance to morphine in the plexus proceed in parallel with loss of subsensitivity to catecholamines and loss of supersensitivity to 5-HT? (c) Would such reversion to normal in the plexus be concurrent with disappearance of CNS indications of tolerance and dependence?

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References

  1. Goldstein, A., and Schulz, R., Br. J. Pharmac., 48, 655–666 (1973).

    Article  CAS  Google Scholar 

  2. Schulz, R., and Goldstein, A., Nature, 244, 168–170 (1973).

    Article  ADS  CAS  Google Scholar 

  3. Gibson, R. D., and Tingstad, J. E., J. pharm. Sci., 59, 426–427 (1970).

    Article  CAS  Google Scholar 

  4. Rang, H. P., Br. J. Pharmac. Chemother., 22, 356–365 (1964).

    Article  CAS  Google Scholar 

  5. Paton, W. D. M., and Zar, M. A., J. Physiol., Lond., 194, 13–33 (1968).

    Article  CAS  Google Scholar 

  6. Goldstein, A., in Proc. International Symposia on Alcohol and Drug Research, Toronto, 1973 (Alcoholism and Drug Addiction Research Foundation, Toronto, in the press).

  7. Goldstein, A., and Sheehan, P., J. Pharmac. exp. Ther., 169, 175–184 (1969).

    CAS  Google Scholar 

  8. Way, E. L., Loh, H. H., and Shen, F. H., J. Pharmac. exp. Ther., 167, 1–8 (1969).

    CAS  Google Scholar 

  9. Cheney, D. L., and Goldstein, A., Nature, 232, 477–478 (1971).

    Article  ADS  CAS  Google Scholar 

  10. Wei, E., and Loh, H., Nature, 238, 396–397 (1972).

    Article  ADS  CAS  Google Scholar 

  11. Cochin, J., and Kornetsky, C., J. Pharmac. exp. Ther., 145, 1–10 (1964).

    CAS  Google Scholar 

  12. Gianutsos, G., Hynes, M. D., Puri, S. K., Drawbaugh, R. B., and Lal, H., Psychopharmacologia, 34, 37–44 (1974).

    Article  CAS  Google Scholar 

  13. Himmelsbach, C. K., Arch. intern. Med., 69, 766–772 (1942).

    Article  Google Scholar 

  14. Martin, W. R., and Jasinski, D. R., J. psychiatr. Res., 7, 9–17 (1969).

    Article  CAS  Google Scholar 

  15. Collier, H. O. J., Nature, 205, 181–182 (1965).

    Article  ADS  CAS  Google Scholar 

  16. Schulz, R., and Cartwright, C., J. Pharmac. exp. Ther. (in the press).

  17. Opitz, K., and Reimann, I., Psychopharmacologia, 28, 165–170 (1973).

    Article  CAS  Google Scholar 

  18. Dixon, W. J., J. Am. stat. Assoc., 60, 967–978 (1965).

    Article  Google Scholar 

Download references

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SCHULZ, R., CARTWRIGHT, C. & GOLDSTEIN, A. Reversibility of morphine tolerance and dependence in guinea pig brain and myenteric plexus. Nature 251, 329–331 (1974). https://doi.org/10.1038/251329a0

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