Scheduled access to ethanol results in motor impairment and tolerance in female C57BL/6J mice
Scheduled access to ethanol results in motor impairment and tolerance in female C57BL/6J mice
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DOI：
10.1016/j.pbb.2005.07.005
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Crabbe, JC
中科院分区：
文献类型：
--
作者：
Cronise, K;Finn, DA;Crabbe, JC
我们最近报道了一种方法，其中限制水的小鼠预定获得乙醇，然后获得水。C57 BL/6 J小鼠将重复自我施用乙醇，其量产生高且稳定的血液乙醇浓度（BEC）[Finn DA，Belknap JK，Cronise K，Yoneyama N，Murillo A，Crabbe X.一个程序，以产生高酒精摄入量的小鼠。Psychopharmacol 2005;178：471-480]。这里报道的研究表明，运动障碍的行为迹象是由这些高酒精摄入引起的，并且有一些证据表明，在重复的训练中，耐受性得到了发展。允许雌性C57 BL/6 J小鼠接触乙醇（5%v/v）30分钟，然后接触水2.5小时：每3天一次，持续12天;每2天一次，持续28天;或每2天一次，持续9天。在中间的几天，小鼠有3小时的水。对照组每天只喝水。小鼠在30分钟内消耗2-2.5 g/kg乙醇，导致1.4-1.5 mg/ml的BEC。运动障碍评估使用加速或固定速度旋转杆，平衡木或屏幕测试。在所有研究中，在接触乙醇或水30分钟后立即测试小鼠的运动损伤。在实验1中，与对照组相比，暴露于乙醇的小鼠从固定速度旋转杆上落下的时间较短，并且在平衡木上的脚滑动较多，表明运动障碍。在饮用乙醇后，小鼠从屏幕上掉下来的速度也比清醒的训练前更快。在实验2中，在6.5和10 RPM的固定速度旋转杆上测试（没有预先训练）运动损伤和耐受性的小鼠在乙醇组中显示重复的运动损伤，但没有产生耐受性。在实验3中，首先以10 RPM对小鼠进行转棒训练。在每个液体获取期后，与对照小鼠相比，以10 RPM自我施用乙醇的小鼠的性能受损，但不是15 RPM。没有证据表明在几天内有耐受性。然而，在最后一天，腹腔注射2 g/kg乙醇后，所有小鼠均以两种RPM进行测试。乙醇经历的小鼠在两种RPM下的受损程度低于乙醇未处理的小鼠，表明根据该组间指数的耐受性发展。这些结果表明，C57 BL/6 J小鼠将反复消耗酒精的量，产生运动障碍，在这些预定的液体访问条件下，和适度的耐受性可以使用适当的测试检测。爱思唯尔公司出版
We recently reported a method where water-restricted mice were given scheduled access to ethanol followed by access to water. C57BL/ 6J mice would repeatedly self-administer ethanol in amounts that produced high and stable blood ethanol concentrations (BEC) [Finn DA, Belknap JK, Cronise K, Yoneyama N, Murillo A, Crabbe X. A procedure to produce high alcohol intake in mice. Psychopharmacol 2005;178:471-480]. The studies reported here demonstrate that behavioral signs of motor impairment result from these high alcohol intakes, and that there was some evidence of tolerance development across repeated sessions. Female C57BL/6J mice were allowed 30 min access to ethanol (5% v/v) followed by 2.5 h access to water either: every 3rd day for 12 days-, every 2nd day for 28 days; or every 2nd day for 9 days. On intervening days, mice had 3 h access to water. A control group had daily access to water only. Mice consumed 2-2.5 g/kg ethanol in 30 min, resulting in BECs of 1.4-1.5 mg/ml. Motor impairment was assessed using the accelerating or fixed speed rotarod, balance beam or screen test. In all studies, mice were tested for motor impairment immediately after 30 min access to ethanol or water. In Experiment 1, ethanol-exposed mice had shorter latencies to fall from the fixed speed rotarod and more foot slips on the balance beam than the control group, indicating motor impairment. After drinking ethanol, mice also fell from a screen more quickly than during sober pretraining. In Experiment 2, mice tested (without prior training) for motor impairment and tolerance on the fixed speed rotarod at 6.5 and 10 RPM showed repeated motor impairment in the ethanol group, but did not develop tolerance. In Experiment 3, mice were first given rotarod training at 10 RPM. Following each fluid access period, performance was impaired in mice self-administering ethanol at 10, but not 15 RPM, when compared to control mice. There was no evidence of tolerance across days. However, on the last day, all mice were tested at both RPM following an i.p. injection of 2 g/kg ethanol. Ethanol-experienced mice were less impaired at both RPM than the ethanol-naive mice, indicating tolerance development according to this between-groups index. These results suggest that C57BL/6J mice will repeatedly consume alcohol in amounts that produce motor impairment under these scheduled fluid access conditions, and that a modest degree of tolerance can be detected using appropriate tests. Published by Elsevier Inc.