Tolerance to the discriminative stimulus effects of ethanol following chronic inhalation exposure to ethanol in C57BL/6J mice
Tolerance to the discriminative stimulus effects of ethanol following chronic inhalation exposure to ethanol in C57BL/6J mice
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DOI：
10.1097/00008877-200412000-00005
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发表时间：
2004-12-01
影响因子：
1.6
通讯作者：
Becker, HC
中科院分区：
文献类型：
--
作者：
Crissman, AM;Studders, SL;Becker, HC
慢性乙醇（EtOH）暴露的一个重要后果是耐受性的发展。本研究旨在研究慢性EtOH暴露后对EtOH辨别性刺激特性的耐受性。训练成年雄性C57 BL/6 J小鼠辨别EtOH（1.00 g/kg; i. p.）从生理盐水中，使用食物强化的两个杠杆操作任务。在获得和建立标准区分性能后，进行了一系列泛化测试，以生成基线EtOH剂量-反应曲线，计算的ED 50剂量为0.42 g/kg。然后将小鼠置于对照（空气）或EtOH吸入室中64 h。在实验1中，歧视性刺激泛化测试与EtOH ED 50剂量进行慢性EtOH（或空气）暴露后24小时没有产生显着不同的EtOH响应，虽然对EtOH线索（耐受性）的敏感性降低的趋势是明显的。In.实验2，采用累积给药程序（ED 50 = 0.37 g/kg），得到基线EtOH剂量-反应函数，计算的ED 50剂量为0.37 g/kg。在慢性EtOH暴露后24 h，重新测定EtOH剂量-反应曲线显示显著向右偏移，与对照空气暴露条件（ED 50 = 0.49 g/kg）相比，ED 50值（ED 50 = 1.09 g/kg）增加了两倍以上。在吸入治疗后48小时（ED 50 = 0.51 g/kg），慢性EtOH暴露小鼠对EtOH提示的明显耐受性消失。这些结果表明，在吸入室中长期暴露于EtOH后，C57 BL/6 J小鼠对EtOH的区别性刺激效应具有耐受性。行为药理学15：569-575（C）2004 Lippincott威廉姆斯威尔金斯。
A significant consequence of chronic ethanol (EtOH) exposure is the development of tolerance. The present study was designed to investigate tolerance to the discriminative stimulus properties of EtOH following chronic EtOH exposure. Adult male C57BL/6J mice were trained to discriminate EtOH (1.00 g/kg; i.p.) from saline, using a food-reinforced two-lever operant task. Following acquisition and establishment of criterion discrimination performance, a series of generalization tests were conducted to generate a baseline EtOH dose-response curve with a calculated ED50 dose of 0.42 g/kg. Mice were then placed into control (air) or EtOH inhalation chambers for 64 h. In Experiment 1, discriminative stimulus generalization tests with the EtOH ED50 dose conducted 24 h following chronic EtOH (or air) exposure did not yield significantly different EtOH responding, although a trend towards reduced sensitivity to the EtOH cue (tolerance) was evident. In. Experiment 2, a cumulative dosing procedure (ED50 = 0.37 g/kg) was employed, yielding a baseline EtOH dose-response function with a calculated ED50 dose of 0.37 g/kg. At 24 h following chronic EtOH exposure, re-determination of the EtOH dose-response curve revealed a significant shift to the right, with more than a twofold increase in the ED50 value (ED50 = 1.09 g/kg) compared to the control air exposure condition (ED50 = 0.49 g/kg). This apparent tolerance to the EtOH cue dissipated in chronic EtOH-exposed mice tested 48 h following the inhalation treatment (ED50 = 0.51 g/kg). These results demonstrate tolerance to the discriminative stimulus effects of EtOH in C57BL/6J mice following chronic EtOH exposure in inhalation chambers. Behavioural Pharmacology 15:569-575 (C) 2004 Lippincott Williams Wilkins.