Reversal of Ethanol Tolerance and Cross-Tolerance to Pentobarbital in the Rat

  • J. M. Khanna
  • H. Kalant
  • A. D. Lê
  • A. E. LeBlanc


Adult male Wistar rats were fed nutritionally adequate liquid diets providing 35% of the total calories as ethanol, while pair-fed controls received the corresponding diet with ethanol replaced by an equicaloric concentration of sucrose. After 2, 4, 6, 8, 10 and 14 weeks of chronic ethanol treatment, separate groups of rats were injected with a test dose of either ethanol (3 g/kg) or pentobarbital (40 mg/kg). Rectal temperatures were determined prior to and at 30, 60, 90 and 120 min after injection. The fall in rectal temperature after a test dose of ethanol or pentobarbital was significantly lower at 2 and 4 weeks in ethanol-treated rats than in pair-fed controls. After 6 and 8 weeks of chronic ethanol treatment, the fall in temperature after the same test doses was still less in ethanol-treated rats than in controls. However, at 10 and 14 weeks the fall in temperature was virtually identical in the two groups. A similar pattern of results was obtained when ethanol-induced sleep was compared in ethanol-treated rats and control rats. These intriguing results challenge the generally believed concept that tolerance and cross-tolerance, once produced, are sustained with chronic treatment, and may raise the possibility that such processes are reversible even during chronic treatment, at least under certain regimens.


Rectal Temperature Test Dose Liquid Diet Chronic Ethanol Ethanol Tolerance 
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  1. Esser, P. H-., 1963, Hangover symptoms, Br.,T. Addict., 59: 65.Google Scholar
  2. Fehr, K. A., Kalant, H. and LeBlanc, A. E., 1976, Residual learning deficits after heavy exposure to cannabis or alcohol in rats, Science (Washington), 192: 1249.CrossRefGoogle Scholar
  3. Hawkins, R. D., Kalant, H. and Khanna, J. M., 1966, Effect of chronic intake of ethanol on rate of ethanol metabolism, Can. J. Physiol. Pharmacol., 44: 241.Google Scholar
  4. Jellinek, E. M., 1960, “The Disease Concept of Alcoholism,” Hillhouse Press, New Haven.Google Scholar
  5. Kalant, H., 1977, Comparative aspects of tolerance to, and dependence on, alcohol, barbiturates and opiates, in: “Alcohol Intoxication and Withdrawal - IIIb,” M. M. Gross, ed., Plenum Press, New York.Google Scholar
  6. Kalant, H., LeBlanc, A. E. and Gibbins, R. J., 1971, Tolerance to, and dependence on, some non-opiate psychotropic drugs, Pharmacol. Rev., 23: 135.Google Scholar
  7. Khanna, J. M. and Kalant, H., 1970, Effect of inhibitors and inducers of drug metabolism on ethanol metabolism in vivo, Biochem. Phar Pharmacol., 19: 2033.Google Scholar
  8. Khanna, J. M., Kalant, H. and Bustos, G., 1967, Influence of sex and of schedule of ethanol administration on liver alcohol dehydrogenase activities, Can. J. Physiol. Pharmacol., 45: 777.Google Scholar
  9. Khanna, J. M., Israel, Y. and Kalant, H., eds., 1975, “Alcoholic Liver Pathology,” Addiction Research Foundation of Ontario, Toronto, Canada.Google Scholar
  10. LeBlanc, A. E., Matsunaga, M. and Kalant, H., 1976, Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats, Pharmacol. Biochem. Behay., 4: 175.Google Scholar
  11. LeBlanc, A.E., Poulos, C. X. and Cappell, H. D., 1977, Tolerance as a behavioral phenomenon: evidence from two experimental paradigms, in: “Behavioral Tolerance: Research and Treatment Implications,” N. A. Krasnegor, ed., NIDA Monograph 18, U.S. Government Printing Office, Washington, D.C.Google Scholar
  12. Lieber, C. S., Jones, D. P., Mendelson, J. and DeCarli, L. M., 1963, Fatty liver, hyperlipemia and hyperuricemia produced by prolonged alcohol consumption despite adequate dietary intake, Trans. Assoc. Amer. Physicians, 76: 289Google Scholar
  13. Merkel, K. L., 1959, Alkoholismus and Alkoholabusus in der Heilstätte, Beitr. Klin. Tuberk., 121: 480.Google Scholar
  14. Parsons, O. A., 1977, Neuropsychological deficits in alcoholisc: facts and fancies, Alcoholism: Clin. Exp. Res., 1: 51.Google Scholar
  15. Peck, R. E., 1949, Alcohol intolerance, J. Am. Med. Assoc., 140: 1192.Google Scholar
  16. Pyatnitskaya, I. N., 1966, Dinamika formirovaniya simptomov narkcm3anicheskoi zavismosti, na primere khronicheskogo alkogolizma, Vop. Psikhiat. Nevropat., 12: 378.Google Scholar
  17. Rankin, J. G., ed., 1975, “Alcohol, Drugs and Brain Damage,” Addiction Research Foundation of Ontario, Toronto, Canada.Google Scholar
  18. Riley, J. N. and Walker, D. W., 1978, Morphological alterations in hippocampus after long-term alcohol consumption in mice, Science (Washington), 201: 646.CrossRefGoogle Scholar
  19. Smith, C. M., 1977, The pharmacology of sedative hypnotics, alcohol and anesthetics: sites and mechanisms of action, in: “Handbuch der experimentellen Pharmakologie, Vol. 45, Part I,” W. R. Martin, ed., Springer-Verlag, Berlin.Google Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • J. M. Khanna
    • 1
  • H. Kalant
    • 1
  • A. D. Lê
    • 1
  • A. E. LeBlanc
    • 1
  1. 1.Department of PharmacologyUniversity of Toronto Addiction Research Foundation of OntarioTorontoCanada

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