Finn Deborah A, Belknap John K, Cronise Kim, Yoneyama Naomi, Murillo Andrea, Crabbe John C
Portland Alcohol Research Center, VAMC Research and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Psychopharmacology (Berl). 2005 Apr;178(4):471-80. doi: 10.1007/s00213-004-2039-8. Epub 2004 Nov 3.
While prolonged access to ethanol (EtOH), or deprivations, or their combination have occasionally been shown to yield high levels of voluntary self-administration, in almost all cases, rodents do not self-administer alcohol to the degree that they will develop substantial, intoxicating blood alcohol levels and then continue to self-administer at these levels.
The purpose of the present series of experiments was to modify a fluid restriction procedure to demonstrate consistent, high EtOH consumption.
Male and female mice from an alcohol preferring inbred strain (C57BL/6J; B6) as well as from a genetically heterogeneous strain (WSC) were given varying periods of access to fluid, ranging from 90 min to 10 h per day, for 12-21 days. Every 3rd or 4th day, separate groups of mice were offered a 5, 7 or 10% EtOH solution for either 10 min or 30 min, followed by water for the remainder of the time.
In all studies, stable high EtOH doses were consumed by both B6 and WSC mice across the EtOH sessions, exceeding 2 g/kg in a 30-min session. Mean blood EtOH concentration exceeded 1 mg/ml (i.e. 100 mg%), with values in individual animals ranging from 0.6 mg/ml to 3.4 mg/ml. Notably, mice receiving 10 h of fluid/day continued to consume 2 g/kg doses of EtOH. While this procedure did not produce subsequent preference for EtOH in WSC mice, consumption remained high in some animals.
These data indicate that scheduling fluid intake produces high, stable EtOH consumption and BEC in male and female B6 and WSC mice.
虽然偶尔有研究表明,长时间接触乙醇(EtOH)、戒断或二者结合会导致高水平的自愿自我给药,但在几乎所有情况下,啮齿动物自我给药酒精的程度都不会使其血液酒精水平达到足以产生显著醉酒效果,然后在这些水平上继续自我给药。
本系列实验的目的是修改液体限制程序,以证明持续的高EtOH消耗量。
给来自酒精偏好近交系(C57BL/6J;B6)以及遗传异质系(WSC)的雄性和雌性小鼠提供不同时间段的液体摄入机会,每天90分钟至10小时,持续12 - 21天。每隔3天或4天,给不同组的小鼠提供5%、7%或10%的EtOH溶液10分钟或30分钟,其余时间提供水。
在所有研究中,B6和WSC小鼠在整个EtOH实验过程中都消耗了稳定的高EtOH剂量,在30分钟的实验中超过2 g/kg。平均血液EtOH浓度超过1 mg/ml(即100 mg%),个体动物的值在0.6 mg/ml至3.4 mg/ml之间。值得注意的是,每天接受10小时液体摄入的小鼠继续消耗2 g/kg剂量的EtOH。虽然该程序在WSC小鼠中没有产生对EtOH的后续偏好,但在一些动物中消耗量仍然很高。
这些数据表明,安排液体摄入会使雄性和雌性B6和WSC小鼠产生高且稳定的EtOH消耗量和血液乙醇浓度。