, Volume 52, Issue 2, pp 185–190 | Cite as

Sensitization to cocaine stimulation in mice

  • Louis Shuster
  • Grace Yu
  • Anne Bates
Animal Studies


Repeated administration of cocaine to B6AF1/J mice increased their running response to 20 mg/kg cocaine as much as four-fold over the response to the first injection. After four daily injections, the extent of the increase was proportional to the dose of cocaine that was used for pretreatment. Sensitization persisted for as long as 2 months after the last injection of cocaine. Cocaine-pretreated mice did not show an increased running response to either morphine or d-amphetamine. The response to cocaine was increased two-fold by treatment with morphine, and three-fold by pretreatment with d-amphetamine. Pretreatment with either imipramine or reserpine did not produce sensitization to cocaine. There was no correlation between cocainesensitization and whole-brain catecholamine levels. There were marked differences in both the running response to cocaine and the extent of cocaine sensitization between the parental strains, C57B1/6J and A/J. Experiments with recombinant-inbred lines, derived from C57Bl/6By and BALB/cBy mice, suggest that the initial response to cocaine and the development of sensitization are controlled by different genetic determinants.

Key words

Cocaine Sensitization Running response Mice Stimulation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ansell, G. B., Beeson, M. F.: A rapid and sensitive procedure for the combined assay of noradrenaline, dopamine and serotonin in a single brain sample. Analyt. Biochem. 23, 196–206 (1968)Google Scholar
  2. Bailey, D. W.: Recombinant inbred strains. Transplantation 11, 325–327 (1971)Google Scholar
  3. Bralet, J., Lallemant, A. M.: Influence du traitment par la cocaine sur la synthèse et la libération de la noradrénaline cérébrale. Arch. int. Pharmacodyn. 217, 332–341 (1975)Google Scholar
  4. Dengler, H. G., Spiegel, H. E., Titus, E. O.: Effect of drugs on uptake of nor-epinephrine by cat tissues. Nature (Lond.) 191, 816–817 (1961)Google Scholar
  5. Down, A. W., Eddy, N. B.: The effect of repeated doses of cocaine on the rat. J. Pharmacol. exp. Ther. 46, 199–200 (1932)Google Scholar
  6. Goldstein, A.: Biostatistics: An introductory text, p. 55. New York: Macmillan 1964Google Scholar
  7. Hawks, R. L., Kopin, I. H., Colburn, R. W., Thoa, N. B.: Norcocaine: a pharmacologically active metabolic of cocaine found in brain. Life Sci. 15, 2189–2195 (1974)Google Scholar
  8. Hertting, G., Axelrod, J., Whitby, L. G.: Effect of drugs on the uptake and metabolism of 3H-norepinephrine. J. Pharmacol. exp. Ther. 134, 146–153 (1961)Google Scholar
  9. Iversen, S. D., Iversen, L. L.: Behavioral pharmacology. New York: Oxford University Press 1975Google Scholar
  10. Jaffe, J. H.: Drug addiction and drug abuse. In: The pharmacological basis of therapeutics, L. S. Goodman and A. Gilman, eds., p. 304. New York: MacMillan 1975Google Scholar
  11. Mason, P.: Drug dependence caused by non-narcotics. In: Animal and clinical pharmacologic techniques in drug evaluation, vol. 2, P. E. Siegler and J. H. Moyer III, eds., pp. 383–388 Chicago: Year Book Medical Publishers 1967Google Scholar
  12. Nayak, P. K., Misra, A. L., Mulé, S. J.: Physiological disposition and biotransformation of (3H) cocaine in acute and chronically-treated rats. J. Pharmacol. exp. Ther. 196, 556–569 (1976)Google Scholar
  13. Post, R. M., Kopanda, R. T.: Cocaine, kindling and reverse tolerance. Lancet 1975, 409–410Google Scholar
  14. Post, R. M.: Cocaine psychoses: a continuum model. Amer. J. Psychiat. 132, 225–231 (1975)Google Scholar
  15. Post, R. M.: Rose, H.: Increasing effects of repetitive cocaine administration in the rat. Nature (Lond.) 260, 731–732 (1976)Google Scholar
  16. Seevers, M. H., Deneau, G. A.: Physiological aspects of tolerance and physical dependence. In: Physiological pharmacology, vol. 1, W. S. Root and E. G. Hofmann, eds., p. 629. New York: Academic Press 1963Google Scholar
  17. Sharpless, S. K.: Supersensitivity-like phenomena in the central nervous system. Fed. Proc. 34, 1990–1997 (1975)Google Scholar
  18. Short, P. H., Shuster, L.: Changes in brain norepinephrine associated with sensitization to d-amphetamine. Psychopharmacology 48, 59–67 (1976)Google Scholar
  19. Shuster, L., Webster, G. W., Yu, G.: Increased running response to morphine in morphine-treated mice. J. Pharmacol. exp. Ther. 192, 64–72 (1975a)Google Scholar
  20. Shuster, L., Webster, G. W., Yu, G.: Perinatal narcotic addiction in mice: sensitization to morphine stimulation. Addict. Dis 2, 277–292 (1975b)Google Scholar
  21. Shuster, L., Webster, G. W., Yu, G., Eleftheriou, B. E.: A genetic analysis of the response to morphine in mice: Analgesia and running. Psychopharmacologia (Berl.) 42, 249–254 (1975c)Google Scholar
  22. Smith, C. B.: Enhancement by reserpine and α-methyl dopa of the effects of d-amphetamine upon locomotor activity of mice. J. Pharmacol. exp. Ther. 142, 343–350 (1963)Google Scholar
  23. Tatum, A. L., Seevers, M. H.: Experimental cocaine addiction. J. Pharmacol. exp. Ther. 36, 401–410 (1929)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Louis Shuster
    • 1
  • Grace Yu
    • 1
  • Anne Bates
    • 1
  1. 1.Department of Biochemistry and PharmacologyTufts University School of MedicineBostonUSA

Personalised recommendations