Strain Differences in the Development of Acute Tolerance to Ethanol
C57B1/6 mouse brain serotonin levels were depleted by feeding animals a diet containing no tryptophan. When such mice were injected with ethanol, they were found to lose their righting reflex for significantly longer periods and to have a lower body temperature than control animals. Animals consuming the diet containing no tryptophan metabolized ethanol more slowly than controls. Although daily injections of kynurenine reinstated ethanol metabolism to normal, the duration of loss of righting reflex and the hypothermia induced by ethanol were unaffected by kynurenine pretreatment. Tryptophan (75 mg/kg) administered six hours prior to ethanol injection returned brain serotonin levels to normal in tryptophan-deprived mice. Mice injected with tryptophan were found to respond to ethanol as did the control animals. When brain ethanol levels were determined at the time that the animals lost their righting reflex and when animals regained their righting reflex, tryptophan-deprived mice were found to regain the righting reflex at the same brain ethanol levels as those at which such animals lost their righting reflex. Control animals regained the righting reflex at higher brain ethanol levels than those at which they lost the righting reflex. Tryptophan administration to tryptophan-deprived mice resulted in their regaining the righting reflex at higher ethanol levels than those at which they lost the reflex. Similar experiments were carried out on C3H/HeJ and DBA/J2 mice. The results indicate that C3H mice developed some acute tolerance while DBA mice failed to develop any acute tolerance. The possibility exists that the strain difference in the degree of sensitivity to ethanol observed in these mice may be due to differing abilities to develop acute tolerance.
KeywordsStrain Difference Ethanol Level Ethanol Metabolism Acute Tolerance Blood Ethanol Level
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- Goldberg, L.: Quantitative Studies on Alcohol Tolerance in Man. The Influence of Ethyl Alcohol on Sensory, Motor and Psychological Functions Referred to Blood Alcohol in Normal and Habituated Individuals. Acta Physiol. Scand. 5, Suppl. 16, 1–128 (1943).Google Scholar
- Greengard, P.: Water Soluble Vitamins, in Goodman, L.S. and Gilman, A., The Pharmacological Basis of Therapeutics, MacMillan, Inc., New York, 1549–1563 (1975).Google Scholar
- Mellanby, E.: Alcohol: Its Absorption into and Disappearance from the Blood Under Different Conditions. Special Report Series No. 31, Medical Research Committee, London, 1919.Google Scholar