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 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. 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.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004032:Diet; D004361:Drug Tolerance; D000431:Ethanol / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009243:NAD / Q000378:metabolism; D013045:Species Specificity; D014364:Tryptophan / Q000494:pharmacology
D009243:NAD; D000431:Ethanol; D014364:Tryptophan