Induction of Physical Dependence upon Alcohol in Nonhuman Primates

  • Walter A. Pieper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 56)


Ethanol-induced physical dependence is generally viewed as a concept which is empirically anchored to observations of alcohol intake for a period of time followed by a set of behavioral responses which are reliably associated with the cessation of alcohol intake. As such, it has the logical status of an intervening variable which must be carefully defined in terms of the operations used to measure the antecedent and consequent events which are presumed to be causally related to physical dependence. It is now generally agreed that exposure of an organism to ethanol for a period of time is both a necessary and sufficient antecedent event for the development of physical dependence. Although the underlying biological basis for this condition is not known, it is generally assumed that the presence of ethanol in nervous tissue results in the gradual development of adaptive changes in the functional state of the central nervous system. When ethanol is withdrawn, the functional balance of the system is disturbed, thus producing what is termed the withdrawal reaction. The set of behaviors which are generally observed following ethanol withdrawal constitute the consequent empirical events that must be carefully measured along with the antecedent conditions if the concept of physical dependence is to be meaningfully established. This operational specification of the concept of physical dependence is important because it provides a sound scientific framework within which previous experiments can be evaluated and new research projects planned. Since the measurement process involved in quantifying both antecedent events and consequent behaviors must also be specified, discrepancies in results from different experiments should be more readily understood, thus encouraging more standardization between laboratories in the techniques and procedures used.


Rhesus Monkey Nonhuman Primate Withdrawal Symptom Withdrawal Syndrome Ethanol Intake 
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  1. 1.
    Victor, M. and Adams, R.D.: The effect of alcohol on the nervous system. Res. Pubi. Ass. Res. Nerv. Ment. Dis., 32: 526–573, 1953.Google Scholar
  2. 2.
    Ellis, F.W. and Pick, J.R.: Experimentally induced ethanol dependence in rhesus monkeys. J. PharmacoZ. Exp. Ther., 175: 88–93, 1970.Google Scholar
  3. 3.
    Mello, N.K.: A review of methods to induce alcohol addiction in animals. Pharmacol. Biochem. Behay., 1: 89–101, 1973.CrossRefGoogle Scholar
  4. 4.
    Gibbins, R.J., Kalant, H., LeBlanc, A.E. and Clark, W.: The effects of chronic administration of ethanol on startle thresholds in rats. Psychopharmacologia (Berl.), 19: 9S104, 1971.Google Scholar
  5. 5.
    French, S.W. and Morris, J.R.: Ethanol dependence in the rat induced by non-intoxicating levels of ethanol. Res. Comm. Chem. Pathol. Pharmacol., 4: 221–233, 1972.Google Scholar
  6. 6.
    Ratcliffe, F.: Ethanol dependence in the rat: Its production and characteristics. * Arch. Int. Pharmacodyn., 196: 146–156, 1972.PubMedGoogle Scholar
  7. 7.
    Freund, G. and Walker, D.W.: Sound-induced seizures during ethanol withdrawal in mice. Psychopharmacologia (Berl.), 22: 45–49, 1971.CrossRefGoogle Scholar
  8. 8.
    Hunt, W.A.: Changes in the neuro-excitability of alcohol-dependent rats undergoing withdrawal as measured by pentylenetetrazole seizure threshold. Neuropharmacology, 12: 1097–1102, 1973.PubMedCrossRefGoogle Scholar
  9. 9.
    Allan, F.D. and Swinyard, C.A.: Evaluation of tissue tolerance to ethyl alcohol by alterations in electro-shock seizure threshold in rats. Anat. Rec., 103: 419, 1949.Google Scholar
  10. 10.
    McQuarrie, D.G. and Fingl, E.: Effects of single doses and chronic administration of ethanol on experimental seizures in mice. J. Pharmacol. Exp. Ther., 124: 264–271, 1958.PubMedGoogle Scholar
  11. 11.
    Deneau, G., Yanagita, T. and Seevers, M.H.: Self-administration of psychoactive substances by the monkey. Psychopharmacologia (Berl.), 16: 30–48, 1969.CrossRefGoogle Scholar
  12. 12.
    Yanagita, T. and Takahashi, S.: Dependence liability of several sedative-hypnotic agents evaluated in monkeys. J. Pharmacol. Exp. Ther., 185: 307–316, 1973.PubMedGoogle Scholar
  13. 13.
    Winger, G.D. and Woods, J.H.: The reinforcing property of ethanol in the rhesus monkey: I. Initiation, maintenance and termination of intravenous ethanol-reinforced responding. Annals N.Y. Acad. Sci., 215: 162–175, 1973.CrossRefGoogle Scholar
  14. 14.
    Pieper, W.A. and Skeen, M.J.: Volitional oral intake of ethanol in rhesus monkeys. Fed. Proc., 33: 553, 1974.Google Scholar
  15. 15.
    Myers, R.D., Stoltman, W.P. and Martin, G.E.: Effects of ethanol dependence induced artificially in the rhesus monkey on the subsequent preference for ethyl alcohol. Physiology and Behavior, 9: 43–48, 1972.PubMedCrossRefGoogle Scholar
  16. 16.
    Myers, R.D. and Holman, R.B.: A procedure for eliminating position habit in preference-aversion tests for ethanol and other fluids. Psychon. Sci., 6: 235–236, 1966.Google Scholar
  17. 17.
    Pieper, W.A., Skeen, M.J., McClure, H.M. and Bourne, P.G.: The chimpanzee as an animal model for investigating alcoholism. Science, 176: 71–73, 1972.PubMedCrossRefGoogle Scholar
  18. 18.
    Pieper, W.A. and Skeen, M.J.: Induction of physical dependence on ethanol in rhesus monkeys using an oral acceptance technique. Life Sciences, 11: part 1, 989–997, 1972.Google Scholar
  19. 19.
    Pieper, W.A. and Skeen, M.J.: A versatile liquid diet for nonhuman primates. Laboratory Animal Science, 22: 916–918, 1972.PubMedGoogle Scholar
  20. 20.
    Victor, M.: Treatment of alcoholic intoxication and the withdrawal syndrome. A critical analysis of the use of drugs and other forms of therapy. Psychosomatic Medicine, 28: (No. 4, Pt. 2), 636–650, 1966.Google Scholar
  21. 21.
    Mello, N.K. and Mendelson, J.H.: The effects of drinking to avoid shock on alcohol intake in primates. In: Biological Aspects of Alcohol, M.K. Roach, W.M. Mclsaac and P.J. Creaven (eds.), University of Texas Press, Austin, pp. 313–340, 1971.Google Scholar
  22. 22.
    Mello, N.K. and Mendelson, J.H.: Evaluation of a polydipsia technique to induce alcohol consumption in monkeys. Physiology and Behavior, 7: 827–836, 1971.PubMedCrossRefGoogle Scholar
  23. 23.
    Mendelson, J.H. and Mello, N.K.: Studies of the development of alcohol addiction in infant monkeys. Annals. N.Y. Acad. Sci., 215: 145–161, 1973.CrossRefGoogle Scholar
  24. 24.
    Woods, J.H. and Winger, G.D.: A critique of methods for inducing ethanol self-intoxication in animals. In: Recent Advances in Studies of Alcoholism, N.K. Mello and J.H. Mendelson (eds.), U.S. Govt. Printing Office, Washington, D.C., Publ. No. (HSM) 71–9045, pp. 413–436, 1971.Google Scholar
  25. 25.
    Lester, D. and Freed, E.X.: Criteria for an animal model of alcoholism. Pharmacol. Biochem. Behay., 1: 103–107, 1973.CrossRefGoogle Scholar
  26. 26.
    Ogata, H., Ogato, F., Mendelson, J.H. and Mello, N.K.: A comparison of techniques to induce alcohol dependence and tolerance in the mouse. J. Pharmacol. Exp. Ther., 180: 216–230, 1972.PubMedGoogle Scholar
  27. 27.
    Goldstein, D.B.: Relationship of alcohol dose to intensity of withdrawal signs in mice. J. Pharmacol. Exp. Ther., 180: 203–215, 1972.PubMedGoogle Scholar
  28. 28.
    Kalant, H.A., LeBlanc, A.E. and Gibbins, R.J.: Tolerance to, and dependence on, some nonopiate psychotropic drugs. Pharmac. Rev., 23: 135–191, 1971.Google Scholar
  29. 29.
    Pieper, W.A. and Skeen, M.J.: Development of functional tolerance to ethanol in rhesus monkeys Macaca mulatta. Pharmacol. Biochem. Behay., 1: 289–294, 1973.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Walter A. Pieper
    • 1
  1. 1.Georgia State University and Yerkes Regional Primate Research CenterEmory UniversityUSA

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