Skip to main content
Log in

Development and loss of tolerance to morphine in the rat

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The development of a differential tolerance to morphine was investigated with respect to the mean effective dose, the threshold dose of tolerance, the degree of tolerance after a fixed dose, and the speed of tolerance loss. The mean effective doses, the threshold doses of tolerance, and the degree of tolerance differed considerably from effect to effect, whereas in all tests tolerance loss remained the same. The mean effective doses were not correlated to threshold doses of tolerance, degree of tolerance, or to the loss of tolerance, but a strong correlation exists between threshold doses of tolerance and degree of tolerance to all effects measured. Consequences of these results upon current theories of tolerance are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Campbell RC (1971) Statische Methoden für Biologie und Medizin. Thieme, Stuttgart

    Google Scholar 

  • Cavalli-Sforza L (1969) Biometrie, Fischer, Stuttgart

    Google Scholar 

  • Collier HOJ, Francis PL (1978) A pharmacological analysis of opiate tolerance/dependence. Life Sci 8:281–298

    Google Scholar 

  • Eddy NB, Leimbach D (1953) Synthetic analgesics. II. Dithenylbutanol and dithenylbutylamines. J Pharmacol Exp Ther 107:385–393

    Google Scholar 

  • Feinberg MP, Cochin J (1972) Inhibition of development of tolerance to morphine by cycloheximide. Biochem Pharmacol 21:3082–3085

    Google Scholar 

  • Fernandes M, Kluwe S, Coper H (1977a) Quantitative assessment of tolerance to and dependence on morphine in mice. Naunyn-Schmiedeberg's Arch Pharmacol 297:53–60

    Google Scholar 

  • Fernandes M, Kluwe S, Coper H (1977b) The development of tolerance to morphine in the rat. Psychopharmacology 54:197–201

    Google Scholar 

  • Ho IK, Lu SE, Stolmann S, Loh HH, Way EL (1972) Influence of p-chloro-phenylalanine on morphine tolerance, physical dependence and regional brain serotonin turnover studied in morphinetolerant dependent mice. J Pharmacol Exp Ther 182:155–165

    Google Scholar 

  • Ho IK, Loh HH, Bhargava HN, Way EL (1975) Effect of cyclic nucleotides and phosphodiesterase inhibition on morphine tolerance and physical dependence. Life Sci 16:1895–1900

    Google Scholar 

  • Kalant H, Le Blanc AE, Gibbins RJ (1971) Tolerance to and dependence on some non-opiate psychotropic drugs. Pharmacol Rev 23:135–191

    Google Scholar 

  • Kalant H (1977) Comparative aspects of tolerance to and dependence on alcohol, barbiturates and opiates. In: Gross ML (ed) Alcohol intoxication and withdrawal, vol 313. Plenum, New York, pp 169–185

    Google Scholar 

  • Kalant H (1978) Behavioural criteria for tolerance and physical dependence. Life Sci 8:281–298

    Google Scholar 

  • Mucha RF, Niesink R, Kalant H (1978) Tolerance to morphine analgesia and immobility measured in rats by changes in log dose-response curves. Life Sci 23:357–369

    Google Scholar 

  • Mucha RF, Kalant H, Linseman MA (1979) Quantitative relationships among measures of morphine tolerance and physical dependence in the rat. Pharmacol Biochem Behav 10:397–405

    Google Scholar 

  • van Ree JM, deWied D (1976) Prolyl-leucyl-glycinamide (PLG) facilitates morphine dependence. Life Sci 19:1331–1340

    Google Scholar 

  • Takemori AE (1974) Biochemistry of drug dependence. Ann Rev Biochem 43:15–33

    Google Scholar 

  • Wikler A (1976) Aspects of tolerance to and dependence on cannabis. Ann NY Acad Sci 282:126–147

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fernandes, M., Kluwe, S. & Coper, H. Development and loss of tolerance to morphine in the rat. Psychopharmacology 78, 234–238 (1982). https://doi.org/10.1007/BF00428157

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00428157

Key words

Navigation