Antagonism of ethanol-induced depression of mouse locomotor activity by hyperbaric exposure

Abstract

Previous studies have shown that exposure to hyperbaric helium + oxygen (HEOX) antagonizes the acute depressant effect of hypnotic doses of ethanol on rodent behavior, precipitates and exacerbates withdrawal in ethanol-dependent mice, and attenuates the development of chronic functional ethanol tolerance. The present study extends these investigations to the sub-hypnotic dose range by determining the effect of hyperbaric exposure on ethanol-induced depression of locomotor activity. Male C57BL/6J mice were given two treatments, 2.5 g/kg ethanol and saline, spaced one week apart according to a within subjects, balanced crossover design. Following injection, animals were exposed individually to 1 atmosphere absolute (ATA) air or to 1 ATA or 12 ATA HEOX inside a 15 liter hyperbaric chamber. Chamber temperatures were adjusted to offset ethanol hypothermia and the cooling effect of helium. Locomotor activity was measured continuously, beginning 10 min after injection, and recorded at prescribed intervals for 60 min. Multivariate analysis of variance of the measured activity revealed statistically significant differences between groups based on atmospheric condition, treatment, and time after injection. Within group comparisons indicated that ethanol treatment induced a significant reduction in locomotor activity in mice exposed to either 1 ATA air or 1 ATA HEOX. In contrast, ethanol-injected mice exposed to 12 ATA HEOX did not show a significant ethanol-induced decrease in locomotor activity, indicating antagonism of ethanol's effect. Hyperbaric exposure did not significantly alter blood ethanol concentrations measured 70 min after ethanol injection, thus making a pharmacokinetic explanation for these results unlikely. These findings are consistent with, and extend, previous evidence suggesting that hyperbaric exposure antagonizes molecular actions of ethanol leading to intoxication.