Intensity and Duration of Chronic Ethanol Exposure Is Critical for Subsequent Escalation of Voluntary Ethanol Drinking in Mice
Intensity and Duration of Chronic Ethanol Exposure Is Critical for Subsequent Escalation of Voluntary Ethanol Drinking in Mice
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DOI：
10.1111/j.1530-0277.2009.01027.x
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发表时间：
2009-11-01
影响因子：
3.2
通讯作者：
Becker, Howard C.
中科院分区：
文献类型：
--
作者：
Griffin, William C., III;Lopez, Marcelo F.;Becker, Howard C.
背景：过度饮酒仍然是一个重要的健康问题。我们实验室和其他实验室最近的研究表明，酒精依赖和复发的动物模型有助于了解导致过度饮酒的因素。在这项研究中，我们测试了酒精暴露的数量和持续时间对于在有限的获取范例中给予酒精的小鼠促进饮酒升级的关键的假设。方法：我们使用了几种慢性间歇性乙醇暴露的方法，这些方法根据血液乙醇浓度(BEC)指示不同的乙醇暴露的数量和持续时间。在使用2小时、2瓶选择饮酒范例建立了小鼠的基线饮酒后，每项研究包括在酒精暴露时期和有限获得乙醇的时期(1个周期)之间交替进行，总共3个周期。在研究1中，小鼠被允许延长接触乙醇的时间(16小时)以口服或留在家中的笼子里。在研究2中，酒精暴露包括以增加剂量的乙醇或等热量蔗糖灌胃作为对照。研究3比较了灌胃联合吡唑(一种酒精脱氢酶抑制剂)和蒸气吸入乙醇的方法，这种方法会增加小鼠的饮酒量。最后，研究4是对我们实验室使用吸入法进行的几项研究的回顾。这项回顾包括一系列蒸汽室后BEC值和乙醇摄入量，这将允许检查饮酒量增加和BEC之间的关系。结果：允许小鼠更长时间饮酒并不会导致在随后的有限接触过程中饮酒量增加。同样，胃管插管产生高BEC(300 mg/dl)的乙醇，无论有没有吡唑，都不会增加饮酒量。只有蒸汽吸入过程导致饮酒量增加，这与整个暴露期间BEC保持在175 mg/dl以上有关。这项回顾性研究提供了进一步的证据，证明持续的BEC水平高于175 mg/dl是导致饮酒增加的关键。结论：我们发现以BEC为指标的酒精暴露的强度(量)和持续时间是导致小鼠饮酒增加的关键。具体地说，BEC必须经常超过175毫克/分升，才会发生饮酒升级。未来的研究将检查神经生物学适应，这可能是慢性间歇性酒精暴露导致的饮酒行为增加的基础。
Background:Excessive alcohol drinking continues to be an important health problem. Recent studies from our laboratory and others have demonstrated that animal models of ethanol dependence and relapse can contribute to understanding factors that contribute to excessive drinking. In this study, we tested the hypothesis that the amount and duration of ethanol exposure is critical for promoting the escalation in drinking by mice given access to ethanol in a limited access paradigm.Methods:We used several methods of chronic intermittent ethanol exposure in male C57BL/6J mice that would vary in the amount and duration of exposure to ethanol as indicated by blood ethanol concentrations (BEC). After establishing baseline drinking in the mice using a 2 hours, 2 bottle choice drinking paradigm, each study involved alternating between periods of ethanol exposure and periods of limited access to ethanol (1 cycle) for a total of 3 cycles. In Study 1, mice were allowed extended access (16 hours) to ethanol for oral consumption or remained in the home cage. In Study 2, the ethanol exposure consisted of intragastric gavage of increasing doses of ethanol or isocaloric sucrose as the control. Study 3 compared intragastric gavage combined with pyrazole, an alcohol dehydrogenase inhibitor, with vapor inhalation of ethanol using procedures known to lead to increased drinking in mice. Finally, Study 4 was a retrospective review of several studies conducted in our laboratory using inhalation procedures. The retrospective review encompassed a range of postvapor chamber BEC values and ethanol intakes that would allow a relationship between increased drinking and BEC to be examined.Results:Allowing mice to drink for longer periods of time did not cause increased drinking in subsequent limited access sessions. Likewise, gastric intubation of ethanol which produced high BEC (> 300 mg/dl) with or without pyrazole did not increase drinking. Only the vapor inhalation procedure, which was associated with sustained BEC above 175 mg/dl for the entire exposure period resulted in increased drinking. The retrospective study provided further evidence that sustained BEC levels above 175 mg/dl was critical to the escalation in drinking.Conclusions:We found that the intensity (amount) and duration of ethanol exposure, indexed by BEC, is critical to produce increased drinking in mice. Specifically, BEC must regularly exceed 175 mg/dl for the escalation in drinking to occur. Future studies will examine neurobiological adaptations that may underlie the increased drinking behavior caused by chronic intermittent ethanol exposure.