Physical dependence on and tolerance to alcohol in the rat

Twenty-four rats of the Holtzman strain were maintained on ad lib food and either a forced-intake regimen of 7 per cent alcohol (v/v) or tap water only from weaning (21 days) until 154 days of age. Upon withdrawal of alcohol most of the alcohol rats were extremely hyperactive and appeared to be engaged in frantic, highly disorganized, exploratory behavior in an open field. The behavior of the water rats was in marked contrast to these data. Alcohol rats were also much less responsive to an injected dose of alcohol than water animals, even though there was no difference in the rate of disappearance of alcohol from the blood. These data suggest the development of a cellular tolerance to alcohol after a chronic exposure period. The intake of alcohol, which appeared to exceed the rats' ability to metabolize it, increased progressively throughout the initial exposure and remained unchanged when water or even a third choice (saccharin) was simultaneously offered. These data would thus seem to suggest that a model for alcohol addiction is possible in the rat which satisfies, for the first time, the classical pharmacologic criteria of addition, i.e. physical dependence, tolerance, etc.