Additive physical dependence: evidence for a common mechanism in alcohol dependence

In previous studies we demonstrated that mice could be made physically dependent with 3 or 6 days inhalation of t-butanol or ethanol vapor. In the present experiments the mice were treated with 3 days of t-butanol followed immediately by 3 days of ethanol at equipotent concentrations, for a total of 6 days continuous exposure. Other mice were given these alcohols in the reverse order. Withdrawal reactions, quantitated by scoring convulsions elicited by handling, were equivalent to those resulting from 6 days exposure to either alcohol alone. One alcohol not only substituted for the other in the maintenance of dependence, but also augmented the abstinence syndrome produced by the first 3 days exposure. An additive effect of ethanol and t-butanol in producing a withdrawal reaction is consistent with the hypothesis of a single underlying mechanism for producing physical dependence on alcohols. This experimental model may be useful for studying cross-dependence.