, Volume 77, Issue 1, pp 11–16 | Cite as

Hyperbaric ethanol antagonism in mice: Studies on oxygen, nitrogen, strain and sex

  • Ronald L. Alkana
  • Richard D. Malcolm
Original Investigations


Male and female C57BL/6J and male BALBc/J mice were injected with 3.6 g/kg ethanol or saline and exposed to 1–10 atmospheres absolute (ATA) air, to 1 ATA 80% helium-20% oxygen, or to 12 ATA helium-oxygen having oxygen partial pressures between 0.5 and 18 times normal. Hyperbaric helium-oxygen significantly reduced sleep-time and increased wake-up brain ethanol concentrations in all mice tested. The degree of antagonism was not enhanced by increasing the oxygen partial pressure. Hyperbaric air increased sleep-time and decreased wake-up brain ethanol concentration in C57 mice. Hyperbaric air induced a pressure-related lethal effect beginning at 6 ATA in intoxicated BALBs. These findings demonstrate that hyperbaric ehanol antagonism extends across strains and sexes, that the degree of antagonism cannot be enhanced by increasing the oxygen partial pressure, and that air is not suitable as an antagonistic hyperbaric gas. The findings are consistent with membrane theories of anesthesia.

Key words

Ethanol Ethanol antagonists Ethanol narcosis Hyperbaric pressure Inert gas narcosis Oxygen toxicity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alkana RL, Malcolm RD (1980a) Antagonism of ethanol narcosis in mice by hyperbaric pressures of 4–8 atmospheres. Alcoholism: Clin Exp Res 4:350–353Google Scholar
  2. Alkana RL, Malcolm RD (1980b) The effects of low level hyperbaric treatment on acute ethanol intoxication. Adv Exp Med Biol 126:499–507Google Scholar
  3. Alkana RL, Malcolm RD (1981) Low level hyperbaric ethanol antagonism in mice: Dose and pressure response. Pharmacology 22:199–208Google Scholar
  4. Alkana RL, Noble EP (1979) Reversal of acute ethanol intoxication in humans. In: Majchrowicz E, Noble EP (eds) Biochemistry and pharmacology of ethanol, vol 2. Plenum Press, New York, pp 349–373Google Scholar
  5. Behenke AR, Thomson RM, Motely EP (1935) The psychologic effect from breathing air at 4 atmospheres pressure. Am J Physiol 112:554–558Google Scholar
  6. Bennett PB, Simon S, Katz Y (1975) High pressures of inert gases and anesthesia mechanisms. In: Fink RB (ed) Molecular mechanism of anesthesia, progress in anesthesiology, vol 1. Raven Press, New York, pp 367–402Google Scholar
  7. Bennett PB (1975) Inert gas narcosis. In: Bennett PB, Elliot DM (eds) The physiology and medicine of diving and compressed air work. Williams and Wilkins, Baltimore, pp 207–230Google Scholar
  8. Chin JH, Goldstein DB (1977) Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol 13:435–441Google Scholar
  9. Damjanovich RP, MacInnes JW (1973) Factors involved in ethanol narcosis: Analysis in mice of three inbred strains. Life Sci 13:55–65Google Scholar
  10. Franks NP, Lieb WR (1981) Is membrane expansion relevant to anesthesia? Nature 292:248–251Google Scholar
  11. Halsey MJ, Wardley-Smith B (1975) Pressure reversal of narcosis produced by anesthetics, narcotics and tranquilizers. Nature 257:811–813Google Scholar
  12. Halsey MJ, Wardley-Smith B, Green CJ (1978) Pressure reversal of general anesthesia — a multi-site expansion hypothesis. Br J Anaesth 50:1091–1097Google Scholar
  13. Jamieson D (1966) Effect of high pressure oxygen on the duration of anaesthesia in mice. J Pharm Pharmacol 18:319–320Google Scholar
  14. Johnson FH, Brown DE, Marsland DA (1942) Pressure reversal of the action of certain narcotics. J Cell Comp Physiol 20:269–276Google Scholar
  15. Johnson FH, Flager EA (1950) Hydrostatic pressure reversal of narcotics in tadpoles. Science 112:91–92Google Scholar
  16. Kakihana R, Brown DR, McClearn GE, Tabershaw IR (1966) Brain sensitivity to alcohol in inbred strains of mice. Science 154:1574–1575Google Scholar
  17. Kent DW, Halsey MJ, Eger EI, II, Kent B (1977) Isoflurane anesthesia and pressure antagonism in mice. Anesth Analg 56:97–101Google Scholar
  18. Lever MJ, Miller KW, Paton WDM, Smith EF (1971) Pressure reversal of anesthesia. Nature 231:368–371Google Scholar
  19. MacInnis J, Dickson JG, Lambertson CJ (1967) Exposure of mice to helium-oxygen at pressures to 122 atmospheres. J Appl Physiol 22:694–698Google Scholar
  20. Malcolm RD, Alkana RL (1981) Temperature dependence of ethanol depression in mice. J Pharmacol Exp Ther 217:770–775Google Scholar
  21. Malcolm RD, Alkana RL (1982) Low level hyperbaric ethanol antagonism: Role of temperature, blood and brain ethanol concentrations. Pharmacol Biochem Behav 16:341–346Google Scholar
  22. 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
  23. Membery JH, Link EA (1964) Hyperbaric exposure of mice to pressures of 60 to 90 atmospheres. Science 144:1241–1242Google Scholar
  24. Miller KW, Paton WDM, Smith RA, Smith EB (1973) The pressure reversal of anesthesia and the critical volume hypothesis. Mol Pharmacol 9:131–143Google Scholar
  25. Miller KW, Wilson MW (1978) The pressure reversal of a variety of anesthetic agents in mice. Anesthesiology 48:104–110Google Scholar
  26. Mustala OO, Azarnoff DL (1969) Effect of oxygen tension on drug levels and pharmacological action in the intact animal. Proc Soc Exp Biol Med 132:37–41Google Scholar
  27. Randall CL, Lester D (1974) Differential effects of ethanol and pentobarbital on sleep-time in C57 and BALB mice. J Pharmacol Exp Ther 188:27–33Google Scholar
  28. Small A (1970) The effect of hyperbaric helium-oxygen on the acute toxicity of several drugs. Toxicol Appl Pharmacol 17:250–261Google Scholar
  29. Sun AY (1979) Biochemical and biophysical approaches in the study of ethanol-membrane interaction. In: Majchrowicz E, Noble EP (eds) Biochemistry and pharmacology of ethanol, vol 2. Plenum Press, New York, pp 81–100Google Scholar
  30. Thomas JR (1973) Amphetamine and chlordiazepoxide effects on behavior under increased pressure of nitrogen. Pharmacol Biochem Behav 1:421–426Google Scholar
  31. Thomas JR, Walsh JM (1978) Behavior evaluation of pharmacological agents in hyperbaric air and helium-oxygen. In: Shiling CW, Beckett MW (eds) Proceedings of Sixth Symposium on Underwater Physiology. FASEB, Bethesda, pp 69–77Google Scholar
  32. Wallgren H, Barry H III (1970) Actions of alcohol. Elsevier, AmsterdamGoogle Scholar
  33. Walsh JM, Bursch LS (1977) Reduction of the behavioral effects of Δ 9-tetrahydrocannabinol by hyperbaric pressure. Pharmacol Biochem Behav 7:111–116Google Scholar
  34. Wollman H, Smith TC (1975) The therapeutic gases. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. MacMillan Publishing Co. Inc., New York, pp 881–893Google Scholar
  35. Wood JD (1975) Oxygen toxicity. In: Bennett PB, Elliot DH (eds) The physiology and medicine of diving and compressed air work. Williams and Wilkins, Baltimore, pp 166–184Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Ronald L. Alkana
    • 1
  • Richard D. Malcolm
    • 1
  1. 1.Institute for Toxicology, School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations