, Volume 83, Issue 2, pp 140–146 | Cite as

Electroencephalographic and behavioral correlates in rats during repeated ethanol withdrawal syndromes

  • Flavio Poldrugo
  • O. Carter SneadIII
Original Investigations


Rats chronically implanted with electrodes in the amygdala, thalamus, hippocampus, and cortex were addicted twice, separated by an interval of 2 weeks, with 18 days of ethanol liquid diet. The diet consumption and the blood ethanol levels (BELs) were carefully controlled twice a day during both addictive phases. After ethanol removal the behavioral and electroencephalographic (EEG) changes were continuously monitored for 24 h. During each withdrawal the behavioral and EEG changes appeared at the same time, the EEG changes being of shorter duration Behavioral and EEG changes (primarily in hippocampus) were more severe and of earlier onset during the second withdrawal. In spite of an ethanol liquid diet intake comparable to that of the first addiction, during the ethanol readdiction the BELs were found to fluctuate. The results support the hypothesis of an ethanol withdrawal potentiation through a mechanism of kindling of different brain areas related to the observed BEL fluctuations.

Key words

Ethanol Physical dependence Ethanol withdrawal syndrome EEG withdrawal signs Blood ethanol levels Readdiction Repeated ethanol withdrawals Ethanol potentiation hypothesis 


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  1. Baker TB, Cannon DS (1979) Potentiation of ethanol withdrawal by prior dependence. Psychopharmacology 60:105–110Google Scholar
  2. Ballenger JC, Post RM (1978) Kindling as a model for alcohol withdrawal syndromes. Brit J Psychiat 133:1–14Google Scholar
  3. Begleiter H, Platz A (1972) The effects of alcohol on the central nervous system in humans. In: Kissin B, Begleiter H (eds) The biology of alcoholism, vol 2, Physiology and behavior. Plenum Press, New York, pp 293–343Google Scholar
  4. Branchey M, Rauscher G, Kissin B (1971) Modifications in the response to alcohol following the establishment of physical dependence. Psychopharmacologia 22:314–322Google Scholar
  5. Cannon DS, Baker TB, Berman RF, Atkinson CA (1974) A rapid technique for producing alcohol dependence in the rat. Pharmacol Biochem Behav 2:831–834Google Scholar
  6. Cicero TJ (1979) A critique of animal analogues of alcoholism. In: Majchrowicz E, Noble EP (eds) Biochemistry and pharmacology of ethanol. Plenum Press, New York, pp 533–560Google Scholar
  7. Cicero TJ (1980) Alcohol self-administration, tolerance and withdrawal in humans and animals: theoretical and methodologcal issues. In: Righter H, Crabbe JC (eds) Alcohol tolerance and dependence. Elsevier North-Holland, Amsterdam, pp 1–51Google Scholar
  8. Deneau G, Yanagita T, Seevers MH (1969) Self-administration of psychoactive substances by the monkey. Psychopharmacologia 16:30–48Google Scholar
  9. Ellis FW, Pick JR (1971) Ethanol intoxication and dependence in rhesus monkeys. In: Mello NK, Mendelson JR (eds) Recent advances in studies of alcoholism: an interdisciplinary symposium. U.S. Government Printing Office, Washington, DC.Google Scholar
  10. Erickson CK, Koch KI, McGinity JW (1980) Subcutaneous silastic implants: maintenance of high blood ethanol levels in rats drinking a liquid diet. Pharmacol Biochem Behav 13:781–786Google Scholar
  11. Freund G (1969) Alcohol withdrawal syndrome in mice. Arch Neurol 21:315–320Google Scholar
  12. Geisler RY, Hunter BE, Walker DW (1978) Ethanol dependence in the rat: temporal changes in neuroexcitability following withdrawal. Psychopharmacology 56:287–292Google Scholar
  13. Gibbins RJ, Kalant H, LeBlanc AE, Clark JW (1971) The effects of chronic administration of ethanol on startle threshold in rats. Psychopharmacologia 19:95–104Google Scholar
  14. Goodard GV, McIntyre DC, Leech CK (1969) A permanent change in function resulting from daily electrical stimulation. Exp Neurol 25:295–330Google Scholar
  15. Goldstein DB (1972) Relationship of alcohol dose to intensity of withdrawal signs in mice. J Pharmacol Exp Ther 180:203–215Google Scholar
  16. Goldstein DB (1974) Rates of onset and decay of alcohol physical dependence in mice. J Pharmacol Exp Ther 130:377–383Google Scholar
  17. Goldstein DB, Arnold VW (1976) Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice. J Pharmacol Exp Ther 199:408–414Google Scholar
  18. Greer CA, Alpern HP, Collins AL (1976) Increased CNS sensitivity to flurothyl as a measure of physical dependence in mice following morphine, phenobarbital and ethanol treatment. Life Sci 18:1375–1382Google Scholar
  19. Guerrero-Figueroa R, Rye MM, Gallant DM, Bishop MP (1970) Electrographic and behavioral effects of diazepam during alcohol withdrawal state in cats. Neuropharmacology 9:143–150Google Scholar
  20. Hinson RE, Siegel S (1980) The contribution of pavlovian conditioning to ethanol tolerance and dependence. In: Rigter H, Crabbe JC (eds) Alcohol tolerance and dependence. Elsevier North-Holland, Amsterdam, pp 181–199Google Scholar
  21. Hunt WA (1973) Changes in the neuro-excitability of alcohol-dependent rats undergoing withdrawal as measured by the pentylenetetrazole seizure threshold. Neuropharmacology 72:1097–1102Google Scholar
  22. Hunter BE, Walker DW (1978) Ethanol dependence in the rat: role of extrapyramidal motor systems in the withdrawal reaction. Exp Neurol 62:374–393Google Scholar
  23. Hunter BE, Walker DW (1980) The neural basis of ethanol dependence: is the withdrawal reaction mediated by localized changes in synaptic excitability?. Adv Exp Med Biol 125:251–269Google Scholar
  24. Hunter BE, Boast CA, Walker DW, Zornetzer SF (1973) Alcohol withdrawal syndrome in rats: neural and behavioral correlates. Pharmacol Biochem Behav 1:719–725Google Scholar
  25. Hunter BE, Riley JN, Walker DW, Freund G (1975) Ethanol dependence in the rat: a parametric analysis. Pharmacol Biochem Behav 3:619–629Google Scholar
  26. Hunter BE, Boast CA, Walker DW, Zornetzer SF, Riley JN (1978) Ethanol dependence in the rat: role of non-specific and limbic regions in the withdrawal reaction. Electroencephalogr Clin Neurophysiol 49:483–495Google Scholar
  27. Kalant H, LeBlanc AE, Gibbins RJ (1971) Tolerance to and dependence on some non-opiate psychotropic drugs. Pharmacol Rev 23:135–191Google Scholar
  28. Kalant H, LeBlanc AE, Gibbins RJ, Wilson A (1978) Accelerated development of tolerance during repeated cycles of ethanol exposure. Psychopharmacologia 60:59–65Google Scholar
  29. LeBlanc AE (1968) Microdetermination of alcohol in blood by gasliquid chromatography. Can J Physiol Pharmacol 46:665–667Google Scholar
  30. LeBlanc AE, Cappell HD (1975) Historical antecedents as determinants of tolerance to and dependence upon psychoactive drugs. In: Cappell HD, LeBlanc AE (eds) Biological and behavioral approaches to drug dependence. Addiction Research Foundation. OntarioGoogle Scholar
  31. LeBlanc AE, Kalant H, Gibbins RJ, Berman ND (1969) Acquisition and loss of tolerance to ethanol by the rat. J Pharmacol Exp Ther 168:244–250Google Scholar
  32. Lester D, Freed EX (1973) Criteria for an animal model of alcoholism. Pharmacol Biochem Behav 1:103–107Google Scholar
  33. Liljequist S, Ahlenius S, Engel J (1977) The effect of chronic ethanol treatment on behavior and central monoamines in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 300:205–216Google Scholar
  34. Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43:245–254Google Scholar
  35. Marfaing-Jallat P (1975) In: Sinclair JD, Kiianmaa K (eds) The effects of centrally active drugs on voluntary alcohol consumption. Finn Found Alcohol Stud, Helsinki, pp 49–57Google Scholar
  36. McQuarrie DG, Fingl E (1958) Effects of single doses and chronic administration of ethanol on experimental seizures in mice. J Pharmacol Exp Ther 124:264–271Google Scholar
  37. Mello NK (1972) Behavioral studies on alcoholism. In: Kissin B, Begleiter H (eds) The biology of alcoholism, vol 2, Physiology and behavior. Plenum Press, New York, pp 219–291Google Scholar
  38. Mendelson JH (1972) Biochemical mechanisms of alcohol addiction. In: Kissin B, Begleiter H (eds) The biology of alcoholism, vol 1. Plenum Press, New York, pp 513–544Google Scholar
  39. Mendelson WB, Majchrowicz E, Mirirani N, Dawson S, Gillin JL, Wyatt RJ (1978) Sleep during chronic ethanol administration and withdrawal in rats. J Stud Alcohol 39:1213–1223Google Scholar
  40. Noble EP, Gillies R, Vigran R, Mandel P (1976) The modification of the ethanol withdrawal syndrome in rats by di-n-propylacetate. Psychopharmacologia 46:27–131Google Scholar
  41. Perrin RG, Kalant H, Livingston KE (1975) Electroencephalographic signs of ethanol tolerance and dependence in the cat. Electroencephalogr Clin Neurophysiol 39:157–162Google Scholar
  42. Pieper WA, Skeen MJ (1977) Alcohol withdrawal reactions in rhesus monkeys. In: Gross MM (ed) Alcohol intoxication and withdrawal, vol 3B. Plenum Press, New York, pp 43–55Google Scholar
  43. Pinel JPJ, Van Oot PH, Aveha LF (1975) Identification of the alcohol withdrawal syndrome by repeated brain stimulation. Nature 154:510–511Google Scholar
  44. Ratcliffe F (1972) Ethanol dependence in the rat: its production and characteristics. Arch Int Pharmacodyn Ther 196:146–156Google Scholar
  45. Ritzmann RF, Tabakoff BB (1976) Body temperature in mice: a quantitative measure of alcohol tolerance and physical dependence. J Pharmacol Exp Ther 199:158–170Google Scholar
  46. Walker DW, Zornetzer SF (1974) Alcohol withdrawal in mice: electroencephalographic and behavioral correlates. Electroencephalogr Clin Neurophysiol 36:233–244Google Scholar
  47. Wikler A, Pescor FT, Fraser HF, Isbell H (1956) Electroencephalographic changes associated with chronic alcoholic syndrome and the alcohol abstinence syndrome. Am J Psychiatry 113:106–114Google Scholar
  48. Winger GD, Woods JH (1973) The reinforcing property of ethanol in the rhesus monkey. I. Initiation, maintenance and termination of intravenous ethanol-reinforced responding. Ann NY Acad Sci 215:162–175Google Scholar
  49. Woods JH, Ikomi F, Winger GD (1971) The reinforcing properties of ethanol. In: Roach M, McIsaac W, Creaven P (eds) Biological aspects of alcoholism. University of Texas Press, Austin, pp 371–388Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • Flavio Poldrugo
    • 1
  • O. Carter SneadIII
    • 1
  1. 1.Departments of Pharmacology, Pediatrics and the Neuroscience ProgramUniversity of AlabamaBirminghamUSA

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