CHRONIC INTRAGASTRIC INFUSION PRODUCES TOLERANCE TO ETHANOL IN LS AND SS MICE

Tolerance to ethanol's effects is seen after chronic injections and after chronic treatment with ethanol-containing liquid diets. However, tolerance associated with injections is often associated with environmental cuing (learned tolerance) and liquid diets do not allow for careful control of dose. The studies reported here demonstrate that chronic (3 g/kg every 6 h for 7 days) intragastric infusion of ethanol produces tolerance to ethanol in both LS and SS mice, as measured by sleep time and effects on open field activity and body temperature. LS mice developed more tolerance for all measures than the SS. The rate of ethanol elimination was increased slightly in both the LS and SS mouse lines following chronic ethanol infusion, which suggests that both lines developed a modest metabolic tolerance to ethanol. In contrast, the waking blood ethanol levels were altered only in the LS mice, which argues that some of the tolerance to ethanol seen in the LS mice is pharmacodynamic 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 administration of ethanol, and minimal animal handling that can be associated with drug delivery, thereby reducing the risk of developing learned tolerance to ethanol.