Does cellular tolerance develop to the lethal effect of ethanol in the rat?

Rats were kept intoxicated by forced intragastric administration of a liquid diet containing ethanol for 4 days or 3 weeks. Control animals were pair-fed with the same liquid diet containing starch instead of ethanol. After withdrawal the animals pretreated for 3 weeks showed tolerance to the lethal effect of ethanol as indicated by significantly prolonged survival and higher cerebrospinal fluid ethanol level at death after an oral test dose of 15 g/kg. The tolerance disappeared within a week. Metabolic tolerance, although present, did not prolong the survival of the animals, and the results suggest involvement of cellular tolerance in the central nervous system.