Froehlich J C, Stewart R B, Li T K, Mosemiller A K, McCullough D E, Ho M C, Kisner J M
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124, USA.
Alcohol Clin Exp Res. 2001 Mar;25(3):370-6.
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."
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.
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.
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.
在大鼠单次酒精暴露过程中，由于在可预测的血液酒精浓度（BAC）下测量因变量存在方法学困难，使得对大鼠会话内酒精耐受性的研究受到阻碍。本研究描述了一种在大鼠中维持数小时稳态血液酒精水平的方法，称为“酒精钳夹法”。
将Wistar大鼠的颈动脉植入一根留置导管用于采血，颈外静脉植入另一根用于酒精输注。为了将BAC钳夹在预定水平，首先给大鼠输注一次负荷剂量的酒精以建立所需的或“目标”BAC，然后以等于大鼠酒精代谢速率的速度持续输注酒精。这使得BAC随时间维持在恒定水平。在不同组的大鼠中，将100、200或300mg%的BAC维持数小时。酒精钳夹法应用于对选择性培育的高饮酒量和低饮酒量大鼠的急性（会话内）酒精耐受性研究。用酒精诱导的体温过低来衡量耐受性，会话内酒精耐受性定义为在酒精输注过程中，当BAC维持在恒定水平时体温向基线恢复。
在三个目标BAC水平的每一个水平上，持续酒精输注程序在整个3小时的酒精输注过程中都使BAC维持在稳态。酒精输注导致体温下降，随后在输注过程中体温恢复到基线，这表明会话内酒精耐受性的形成。
持续酒精输注程序（酒精钳夹法）在广泛的血液酒精水平范围内，在个体内和个体间都使BAC维持在稳态。酒精钳夹法似乎是后续大鼠会话内酒精耐受性研究的一种有用工具。
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