Hyperbaric ethanol antagonism: role of temperature, blood and brain ethanol concentrations

Three studies investigated the mechanism of hyperbaric ethanol antagonism. C57 Bl/6j mice were injected intraperitoneally with 3.6 g/kg ethanol and were exposed to 1-12 atmospheres absolute (ATA) helium-oxygen or to 1 ATA air at temperatures that offset the cooling effects of helium or helium and ethanol. Hyperbaric treatment significantly reduced sleep-time and increased wake-up brain ethanol concentrations compared to temperature matched controls. Treatment with 12 ATA helium-oxygen increased the brain ethanol concentration and the brain-blood ethanol ratio at 150 minutes after ethanol administration. These results exclude helium or pressure-induced changes in body temperature, rate of blood ethanol decline or distribution to the brain as mechanisms mediating the antagonism. The data support a membrane site of antagonism.