LOW-LEVEL HYPERBARIC ANTAGONISM OF ETHANOL-INDUCED LOCOMOTOR DEPRESSION IN C57BL 6J MICE - DOSE-RESPONSE/

This study characterized the antagonistic effects of hyperbaric exposu re on the dose-response curve for ethanol-induced depression of locomo tor activity. Drug-naive, male C57BL/6 mice were injected intraperiton eally with saline, 1.5, 2.0, 2.5, or 3.0 g/kg ethanol, and were expose d to 1 atmosphere absolute (ATA) air or 12 ATA helium-oxygen gas mixtu res (heliox) at temperatures that offset the hypothermic effects of et hanol and helium. Locomotor activity was measured 10-30 min after inje ction. In addition, the effects of exposure to 12 ATA heliox on blood ethanol concentrations were tested in a separate group of mice injecte d with 2.5 g/kg ethanol. Ethanol produced a dose-dependent depression of locomotor activity beginning at 2.0 g/kg. Exposure to 12 ATA heliox completely antagonized the locomotor depressant effects of 2.0 and 2. 5 g/kg ethanol and partially blocked the effects of 3.0 g/kg. Activity in mice given 1.5 g/kg ethanol was not significantly affected at 1 AT A air, but was significantly increased at 12 ATA heliox. Low-level hyp erbaric exposure shifted the ethanol dose-response curve to the right with a resultant increase in the ED50 of ethanol for locomotor depress ion from 2.6 to 3.3 g/kg. Exposure to 12 ATA heliox did not alter bloo d ethanol concentrations in mice injected with 2.5 g/kg ethanol. These findings with 12 ATA heliox present key new evidence for the hypothes is that low-level hyperbaric exposure acts directly, with a pattern an alogous to a competitive, mechanistic antagonist of ethanol.