Quantitative comparison of physical dependence on tertiary butanol and ethanol in mice: correlation with lipid solubility.

Mice were made physically dependent on t-butanol and the withdrawal reaction was compared quantitatively with that produced by ethanol. The mice inhaled t-butanol vapor (50-140 mumol/1 of air) continuously for 1, 3, 6 or 9 days. Daily t-butanol blood levels were determined by gas chromatography, using ethanol as internal standard. After t-butanol exposure the mice were removed from the vapor chamber and the withdrawal reaction was quantitated by hourly scoring of convulsions elicited by handling. The peak of the withdrawal reaction occurred 3 to 5 hr after the mice were removed from the t-butanol vapor. The intensity of the withdrawal reaction increased with the duration of inhalation, and with the t-butanol blood levels maintained during the intoxication period. The withdrawal syndrome was qualitatively similar to that produced by ethanol. Quantitatively, t-butanol was 4 to 5 times more potent than ethanol in producing physical dependence. Since t-butanol is about 4 to 5 times more lipid soluble than ethanol, the data are consistent with a cell membrane site for alcohols in producing physical dependence.