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Rates of onset and decay of alcohol physical dependence in mice.

Mice were kept continuously intoxicated by ethanol inhalation for periods of 3 to 12 days. Blood alcohol levels were stabilized by daily injections of pyrazole and by adjusting the alcohol vapor concentrations to offset metabolic tolerance. The magnitude of physical dependence was estimated by scoring the convulsions elicited by handling during the withdrawal period. Physical dependence increased progressively for about 9 days of intoxication, then leveled off. Dependence also varied with the blood alcohol level maintained during intoxication. To measure the rate of decay of physical dependence, mice were given four successive 3-day periods of intoxication separated by brief intervals. If the interval was as long as 24 hours, the withdrawal seizures were no more severe after the fourth cycle of intoxication than after the first, indicating that the dependence accrued within each cycle had decayed completely in 24 hours. When intervals of 3.8 or 12 hours were allowed between cycles, there was partial carryover of dependence into the next cycle. The results indicate that physical dependence develops only during episodes of continuous intoxication and that even 1 day of sobriety suffices for recovery.