Low-level hyperbaric antagonism of ethanol-induced locomotor depression in C57BL/6J mice: dose response.
This study characterized the antagonistic effects of hyperbaric exposure on the dose-response curve for ethanol-induced depression of locomotor activity. Drug-naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, 2.5, or 3.0 g/kg ethanol, and were exposed to 1 atmosphere absolute (ATA) air or 12 ATA helium-oxygen gas mixtures (heliox) at temperatures that offset the hypothermic effects of ethanol and helium. Locomotor activity was measured 10-30 min after injection. In addition, the effects of exposure to 12 ATA heliox on blood ethanol concentrations were tested in a separate group of mice injected 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 ATA air, but was significantly increased at 12 ATA heliox. Low-level hyperbaric exposure shifted the ethanol dose-response curve to the right with a resultant increase in the ED50 of ethanol for locomotor depression from 2.6 to 3.3 g/kg. Exposure to 12 ATA heliox did not alter blood ethanol concentrations in mice injected with 2.5 g/kg ethanol. These findings with 12 ATA heliox present key new evidence for the hypothesis that low-level hyperbaric exposure acts directly, with a pattern analogous to a competitive, mechanistic antagonist of ethanol.
Bejanian
M
M
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
Jones
B L
BL
Alkana
R L
RL
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D006931:Hyperbaric Oxygenation; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*
D000431:Ethanol