Genetic influences on the rate of development of ethanol tolerance and the ethanol physical withdrawal syndrome in mice

A technique is described with which the development of cellular tolerance to ethanol can be followed in mice inhaling ethanol vapour. Cellular tolerance to ethanol's effects on either loss of righting reflex or loss of rotarod performance develops surprising rapidly (approximately 5 hours) in TO Swiss mice. When a comparison was made between strains, mice of the C57BL/6J strain were observed to show very rapid development of cellular tolerance, whereas mice of the DBA2 strain became tolerant to ethanol much more slowly. TO Swiss mice were intermediate. Groups of mice of each strain were then exposed to ethanol vapour for a period of 10 days, such that similar concentrations of ethanol were obtained in the blood of individuals of each strain. Ethanol was withdrawn after this time, and all mice investigated for signs of the ethanol physical withdrawal syndrome. Mice of the C57BL/6J strain showed a brief and mild withdrawal syndrome. DBA2 mice exhibited a severe and prolonged syndrome, whereas mice of the TO Swiss strain were again intermediate. It is suggested that the genetically determined capacity to adapt rapidly to the presence of ethanol (rapid cellular tolerance) is related to the ability to adapt rapidly to the removal of the drug, and that this limits the duration and severity of the ethanol withdrawal syndrome.