Induction of Steady-State Blood Alcohol Levels: Application to the Study of Within-Session Alcohol Tolerance in Rats

Abstract

Background: The study of within-session alcohol tolerance in the rat has been hampered by methodological difficulties related to the measurement of dependent 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 rat, referred to as the “alcohol clamp.” Methods: Wistar rats were implanted with an indwelling catheter in the carotid artery for blood sampling and another in the external jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats first were infused with a priming dose of alcohol to establish the desired or “target” BAC, 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 over 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 acute (within-session) alcohol tolerance in rats selectively bred for high and low alcohol drinking. Alcohol-induced hypothermia was used to index tolerance, and within-session alcohol tolerance was defined as a return of body temperature toward baseline during the course of the alcohol infusion while BAC was maintained at a constant level. Results: The continuous alcohol infusion procedure maintained BAC in a steady state throughout the 3 hr alcohol infusion session at each of the three target BAC levels. Alcohol infusion induced a drop in body temperature, followed by a return of temperature toward baseline during the course of infusion, which indicated the development of within-session alcohol tolerance. Conclusions: The continuous alcohol infusion procedure (alcohol clamp) maintained BAC in a steady state, both within and between subjects, across a wide 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.