Induction of steady-state blood alcohol levels: Application to the study of within-session alcohol tolerance in rats

Background: The study of within-session alcohol tolerance in the rat has be en hampered by methodological difficulties related to the measurement of de pendent variables at predictable blood alcohol concentrations (BAC) during a single session of alcohol exposure. This study characterizes a method for maintaining steady-state blood alcohol levels over several hours in the ra t, referred to as the "alcohol clamp." Methods: Wistar rats were implanted with an indwelling catheter in the caro tid artery for blood sampling and another in the external jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats first were in fused with a priming dose of alcohol to establish the desired or "target" B AG, followed by a continuous infusion of alcohol at a rate equal to that of alcohol metabolism in the rat. This maintained BAC at a constant level ove r time. BACs of 100, 200, or 300 mg% were maintained over several hours in separate groups of rats. The alcohol clamp was applied to the study of acut e (within-session) alcohol tolerance in rats selectively bred for high and low alcohol drinking. Alcohol-induced hypothermia was used to index toleran ce. and within-session alcohol tolerance was defined as a return of body te mperature toward baseline during the course of the alcohol infusion while B AC was maintained at a constant level. Results: The continuous alcohol infusion procedure maintained BAC in a stea dy state throughout the 3 hr alcohol infusion session at each of the three target BAC levels. Alcohol infusion induced a drop in body temperature, fol lowed by a return of temperature toward baseline during the course of infus ion, which indicated the development of within-session alcohol tolerance. Conclusions: The continuous alcohol infusion procedure (alcohol clamp) main tained BAC in a steady state, both within and between subjects, across a wi de range of blood alcohol levels. The alcohol clamp appears to be a useful tool for subsequent studies of within-session alcohol tolerance in the rat.