Effect of duration and pattern of chronic ethanol exposure on tolerance to the discriminative stimulus effects of ethanol in C57BL/6J mice
Effect of duration and pattern of chronic ethanol exposure on tolerance to the discriminative stimulus effects of ethanol in C57BL/6J mice
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DOI：
10.1124/jpet.106.108795
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发表时间：
2006-11-01
影响因子：
3.5
通讯作者：
Baros, Alicia M.
中科院分区：
文献类型：
--
作者：
Becker, Howard C.;Baros, Alicia M.
这项研究的目的是检查长期乙醇暴露的数量和/或模式（间歇或连续）是否会随后改变对乙醇歧视性刺激效应的敏感性。成年雄性 C57BL/6J 小鼠经过训练，能够在两杆食物强化操作程序中区分 1.5 g/kg 乙醇和盐水。一旦成功获得乙醇辨别力，就使用累积剂量程序进行泛化测试，以生成基线剂量反应函数（0-2.5 g/kg 乙醇）。然后暂停辨别训练，同时小鼠在吸入室中接受长期乙醇蒸气或空气暴露。乙醇暴露总量系统性增加，但以间歇或连续方式输送。吸入治疗后 24 或 16 小时，使用相同的概括测试程序重新评估乙醇的辨别能力。结果表明，对照（暴露在空气中）小鼠的辨别能力与基线相似。然而，长期乙醇治疗后对乙醇辨别线索的敏感性降低（剂量反应函数右移和 ED50 值增加证明）。这种耐受效应的程度随着长期接触乙醇的次数以及接触乙醇的总持续时间而增加。此外，在停止长期乙醇治疗后（ED50 值增加 2 至 3 倍）后较早（16 小时与 24 小时）进行泛化测试，耐受性更强。这些结果可能具有重要的临床意义，因为对乙醇辨别线索的敏感性减弱可能有助于在类似的长期乙醇治疗后在这些小鼠中观察到的乙醇自我给药行为增强。
This study was conducted to examine whether amount and/or pattern (intermittent or continuous) of chronic ethanol exposure subsequently alters sensitivity to the discriminative stimulus effects of ethanol. Adult male C57BL/6J mice were trained to discriminate between 1.5 g/kg ethanol and saline in a two-lever food-reinforced operant procedure. Once ethanol discrimination was successfully acquired, generalization testing was conducted using a cumulative dosing procedure to generate a baseline dose-response function (0-2.5 g/kg ethanol). Discrimination training was then suspended while mice received chronic ethanol vapor or air exposure in inhalation chambers. The total amount of ethanol exposure was systematically increased, but it was delivered in an intermittent or continuous manner. At 24 or 16 h after inhalation treatment, ethanol discriminability was reassessed using the same generalization testing procedures. Results indicated that discrimination performance in control (air-exposed) mice was similar to baseline. However, sensitivity to the discriminative cue of ethanol following chronic ethanol treatment was reduced (as evidenced by rightward shifts in the dose-response functions and increased ED50 values). The magnitude of this tolerance effect increased as a function of the number of chronic ethanol exposures as well as the total duration of ethanol exposure. In addition, tolerance was more robust when generalization testing was conducted earlier (16 versus 24 h) after chronic ethanol treatment was halted (2- to 3-fold increase in ED50 values). These results may have important clinical implications, because blunted sensitivity to the discriminative cue of ethanol may contribute to enhanced ethanol self-administration behavior observed in these mice following similar chronic ethanol treatment.