Drug dependence as an adaptive response: studies with ethanol in mice

When mice were kept continuously intoxicated by inhalation of ethanol, physical dependence developed progressively, reaching its maximum in about 2 weeks. Decay of physical dependence during periods of sobriety was complete in about a day. These rapid time courses are consistent with a theoretical model in which alcohol inhibits and simultaneously stabilizes its target. This target may be located in central adrenergic synapses, because interference with function of such synapses facilitated the alcohol withdrawal reaction and because strain differences in withdrawal seizure scores correlated well with strain differences in reserpine effects.