LOW-LEVEL HYPERBARIC EXPOSURE ANTAGONIZES LOCOMOTOR EFFECTS OF ETHANOL AND N-PROPANOL BUT NOT MORPHINE IN C57BL MICE

Low-level hyperbaric exposure antagonizes a broad range of behavioral effects of ethanol in a direct, reversible, and competitive manner. Th is study investigates the selectivity of the antagonism across other d rugs. C57BL/6 mice were injected with saline, ethanol, n-propanol, or morphine sulfate, and then were exposed to 1 atmosphere absolute (ATA) air, 1 ATA helium-oxygen gas mixture (heliox), or 12 ATA heliox. Loco motor activity was measured from 10 to 40 min following injection. N-p ropanol produced a dose-dependent depression of locomotor activity fro m 1.0 g/kg. Morphine produced a dose-dependent stimulation of locomoto r activity at doses of 3.75-12.0 mg/kg. Exposure to 12 ATA heliox sign ificantly antagonized the locomotor depressant effects of 1.0 g/kg n-p ropanol and 2.5 g/kg ethanol, without significantly affecting blood co ncentrations of these drugs measured at 40 min postinjection. Exposure to 12 ATA heliox did not significantly antagonize the locomotor-stimu lating effects of the two morphine doses tested (3.75 and 7.5 mg/kg). These findings suggest that exposure to 12 ATA heliox antagonizes the behavioral effects of intoxicant-anesthetic drugs like ethanol and n-p ropanol, which are believed to act via perturbation or allosteric modu lation of functional proteins, but does not antagonize the effects of drugs like morphine, which act via more direct mechanisms. This demons tration of selective antagonism adds important support for the hypothe sis that low-level hyperbaric exposure is a direct mechanistic ethanol antagonist, with characteristics similar to a competitive pharmacolog ical antagonist.