Genetically Determined Differences in the Antagonistic Effect of Pressure on Ethanol‐Induced Loss of Righting Reflex in Mice

Hyperbaric exposure antagonizes ethanol's behavioral effects in a wide variety of species. Recent studies indicating that there are genetically determined differences in the effects of body temperature manipulation on ethanol sensitivity suggested that genotype might also influence the effects of hyperbaric exposure on ethanol intoxication. To investigate this possibility, ethanol injected long sleep(LS)/lbg (2.7 g/kg), short sleep (SS)/lbg (4.8 g/kg), 129/J (2.9 g/kg), and C57BL/6J (3.6 g/kg) mice were exposed to one atmosphere absolute (ATA) air or to one or 12 ATA helium‐oxygen (heliox) at ambient temperatures selected to offset ethanol and helium‐induced hypothermia. Hyperbaric exposure significantly reduced loss of righting reflex (LORR) duration in LS, 129, and C57 mice, but not in SS mice. A second experiment found that hyperbaric exposure significantly reduced LORR duration and increased the blood ethanol concentration (BEC) at return of righting reflex (RORR) in LS mice, but did not significantly affect either measure in SS mice. These results indicate that exposure to 12 ATA heliox antagonizes ethanol‐induced LORR in LS, 129 and C57 mice, but not in SS mice. Taken with previous results, the present findings suggest that the antagonism in LS, 129, and C57 mice reflects a pressure‐induced decrease in brain sensitivity to ethanol and that the lack of antagonism in SS mice cannot be explained by pressure‐induced or genotypic differences in ethanol pharmacokinetics. The differential sensitivities of SS and LS mice to pressure‐antagonism of ethanol‐induced LORR suggest that hyperbaric exposure can be used as a tool to link differences between these lines in their behavioral and in vitro responses to ethanol and thus may aid in the identification of critical neurochemical mechanisms that underlie intoxication.