Hyperbaric ethanol antagonism: Role of temperature, blood and brain ethanol concentrations

Malcolm, Richard D.; Alkana, Ronald L.

doi:10.1016/0091-3057(82)90169-1

Cited by 41 publications

(22 citation statements)

References 21 publications

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“…In previous studies we observed that exposure to 12 atmospheres absolute (ATA) of a mixture of helium and oxygen antagonizes the acute depressant effect of ethanol in mice (5,(9)(10)(11)(12). The antagonismn does not reflect changes in the absorption, distribution, or elimination of ethanol; increases in the partial pressure of oxygen or helium; or alterations in body temperature.…”

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confidence: 98%

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Ethanol Withdrawal in Mice Precipitated and Exacerbated by Hyperbaric Exposure

Alkana

Finn

Galleisky

et al. 1985

Science

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Mice were fed an ethanol-containing liquid diet for 9 days. On removal of the diet, exposure to 12 atmospheres absolute of a mixture of helium and oxygen precipitated earlier withdrawal, increased withdrawal scores for the first 6 hours, and increased the peak withdrawal intensity compared to dependent animals exposed to control conditions. The enhanced withdrawal did not appear to reflect alterations in ethanol elimination, oxygen or helium partial pressures, body temperature, or general excitability. These results extend to chronically treated animals the evidence that hyperbaric exposure antagonizes the membrane actions of ethanol.

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confidence: 98%

“…We used a higher chamber temperature in the helium + oxygen conditions to offset the cooling effect of helium and thereby eliminate the potential for confounded results due to differences in body temperature (10,14,16). Three 18liter chambers, holding up to seven mice each, were used to test the three treatment conditions simultaneously (17).…”

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confidence: 99%

Ethanol Withdrawal in Mice Precipitated and Exacerbated by Hyperbaric Exposure

Alkana

Finn

Galleisky

et al. 1985

Science

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“…Brains were removed, weighed, homogenized in 10.0 ml ice cold 0.6 N perchloric acid solution containing 10 mM n-propanol, and centrifuged at 1500 rpm for 20 min at 4 ° C. A 200 gl sample of the supernatant was transferred to a serum vial and frozen at -20 ° C until assayed by head-space gas chromatography (Malcolm and Alkana 1982).…”

Section: Methodsmentioning

confidence: 99%

Temperature dependence of ethanol depression in rats

1986

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The relationship between ambient temperature, body temperature, and brain sensitivity to ethanol was investigated in rats. Drug naive male Long Evans rats were injected IP with a hypnotic dose of ethanol (2.75 g/kg, 20% w/v). Immediately after injection, separate groups were exposed to one of five ambient temperatures from 12 to 34 degrees C. Ambient temperature significantly affected wake-up rectal temperature, sleep-time, and wake-up brain ethanol concentration. Sleep-times in individual rats increased 387% (from 24.0 min at 12 degrees C to 116.8 min at 34 degrees C) and wake-up brain ethanol concentrations decreased 79% (from 3.6 mg/g at 12 degrees C to 2.3 mg/g at 34 degrees C) as body temperatures increased from 35 to 41 degrees C. In addition, wake-up rectal temperatures were significantly, positively correlated with sleep-times (r = 0.32, P less than 0.05) and significantly, negatively correlated with wake-up brain ethanol concentrations (r = -0.49, P less than 0.01), further suggesting that brain sensitivity to ethanol increases as body temperature increases. These results are consistent with previous findings in mice, fit membrane perturbation theories of anesthesia, and indicate that temperature dependence of ethanol sensitivity is a general phenomenon extending across species. In conjunction with previous findings, the results also suggest that body temperature during intoxication may participate in mediating species differences in ethanol sensitivity.

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“…These studies at 12 ATA and lower demonstrate that pressure antagonism meets the key criteria for a direct mechanism (Syapin et al , 1988;Bejanian et al , 1993;Davies et al , 1994;Syapin et al , 1996;Davies et al , 1999;Davies and Alkana, 2001;Malcolm and Alkana, 1982;Alkana and Malcolm, 1982b;Alkana and Malcolm, 1982a;Davies et al , 2003) and selectivity (Alkana et al , 1995;Davies and Alkana, 1998;Davies et al , 1996;Davies and Alkana, 1998;Davies et al , 2001;Davies et al , 1999;Davies et al , 2003), necessary for it to be used in a manner analogous to a traditional pharmacological antagonist to help identify initial molecular sites of ethanol action and to test cause-effect relationships (Davies and Alkana, 2001). From this perspective, the sites of pressure antagonism are the same as the sites of ethanol action.…”

Section: Introductionmentioning

confidence: 94%

“…Studies show that exposure to 4–12 times normal atmospheric pressure (ATA) is a direct ethanol antagonist that blocks and reverses a broad spectrum of ethanol’s acute and chronic behavioral effects (Alkana and Malcolm, 1981;Alkana and Malcolm, 1982a;Malcolm and Alkana, 1982;Alkana et al , 1992;Nielsen et al , 1987;Bejanian et al , 1993;Davies et al , 1994;Davies et al , 1999;Davies and Alkana, 2001), as well as its effects at the biochemical (Davies and Alkana, 1998;Davies et al , 1999;Davies and Alkana, 2001) and molecular (Davies et al , 2003;Davies et al , 2004;Perkins et al , 2008) levels.…”

Section: Introductionmentioning

confidence: 99%

Molecular targets and mechanisms for ethanol action in glycine receptors

Perkins¹,

Trudell²,

Crawford³

et al. 2010

Pharmacology & Therapeutics

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Glycine receptors (GlyRs) are recognized as the primary mediators of neuronal inhibition in the spinal cord, brain stem and higher brain regions known to be sensitive to ethanol. Building evidence supports the notion that ethanol acting on GlyRs causes at least a subset of its behavioral effects and may be involved in modulating ethanol intake. For over two decades, GlyRs have been studied at the molecular level as targets for ethanol action. Despite the advances in understanding the effects of ethanol in vivo and in vitro, the precise molecular sites and mechanisms of action for ethanol in ligand-gated ion channels in general, and in GlyRs specifically, are just now starting to become understood. The present review focuses on advances in our knowledge produced by using molecular biology, pressure antagonism, electrophysiology and molecular modeling strategies over the last two decades to probe, identify and model the initial molecular sites and mechanisms of ethanol action in GlyRs. The molecular targets on the GlyR are covered on a global perspective, which includes the intracellular, transmembrane and extracellular domains. The latter has received increasing attention in recent years. Recent molecular models of the sites of ethanol action in GlyRs and their implications to our understanding of possible mechanism of ethanol action and novel targets for drug development in GlyRs are discussed.

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Hyperbaric ethanol antagonism: Role of temperature, blood and brain ethanol concentrations

Cited by 41 publications

References 21 publications

Ethanol Withdrawal in Mice Precipitated and Exacerbated by Hyperbaric Exposure

Ethanol Withdrawal in Mice Precipitated and Exacerbated by Hyperbaric Exposure

Temperature dependence of ethanol depression in rats

Molecular targets and mechanisms for ethanol action in glycine receptors

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