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

J. C. Froehlich, R. B. Stewart, T. K. Li, A. K. Mosemiller, D. E. McCullough, M. C. Ho, J. M. Kisner

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)370-376
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume25
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Blood Alcohol Concentration
  • Steady State

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

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