Rl. Alkana et al., LOW-LEVEL HYPERBARIC EXPOSURE ANTAGONIZES LOCOMOTOR EFFECTS OF ETHANOL AND N-PROPANOL BUT NOT MORPHINE IN C57BL MICE, Alcoholism, clinical and experimental research, 19(3), 1995, pp. 693-700
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.