CHRONIC INTRAGASTRIC INFUSION PRODUCES TOLERANCE TO ETHANOL IN LS ANDSS MICE

Tolerance to ethanol's effects is seen after chronic injections and af ter chronic treatment with ethanol-containing liquid diets. However, t olerance associated with injections is often associated with environme ntal cuing (learned tolerance) and liquid diets do not allow for caref ul control of dose. The studies reported here demonstrate that chronic (3 g/kg every 6 h for 7 days) intragastric infusion of ethanol produc es tolerance to ethanol in both LS and SS mice, as measured by sleep t ime and effects on open field activity and body temperature. LS mice d eveloped more tolerance for all measures than the SS. The rate of etha nol elimination was increased slightly in both the LS and SS mouse lin es following chronic ethanol infusion, which suggests that both lines developed a modest metabolic tolerance to ethanol. In contrast, the wa king blood ethanol levels were altered only in the LS mice, which argu es that some of the tolerance to ethanol seen in the LS mice is pharma codynamic tolerance. Thus, chronic intragastric infusion of ethanol is a reliable method for treating animals chronically with ethanol that allows for the precise control of dose and dose interval, oral adminis tration of ethanol, and minimal animal handling that can be associated with drug delivery, thereby reducing the risk of developing learned t olerance to ethanol.