Development of an alcohol deprivation and escalation effect in C57BL/6J mice
Development of an alcohol deprivation and escalation effect in C57BL/6J mice
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DOI：
10.1111/j.1530-0277.2006.00248.x
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发表时间：
2006-12-01
影响因子：
3.2
通讯作者：
Kalivas, Peter W.
中科院分区：
文献类型：
--
作者：
Melendez, Roberto I.;Middaugh, Lawrence D.;Kalivas, Peter W.
工作背景：通过酒精剥夺效应（ADE）的表达研究了类似复发的饮酒，ADE是通过强制戒酒后乙醇偏好和消费的显著增加来衡量的。尚无研究表征C57 BL/6 J（B6）小鼠中的ADE。本研究探讨了剥夺的长度和数量对ADE在B6 mice.Methods中表达的影响：成年雄性B6小鼠连续24小时接受乙醇和水6周（基线）。实验1测定了每周接受15%乙醇的小鼠中的ADE（即，每周暴露1天，其余6天不暴露），共10周。实验2和3分别测定了接受单一浓度的15%乙醇或多个浓度的7.5%、15%和30%乙醇的小鼠在单一2周剥夺期后的ADE，随后每周获得其各自的乙醇溶液，持续10周。实验4确定的ADE后，一个单一的2周的剥夺期，然后每天获得15%的乙醇。从未剥夺乙醇的小鼠（即，结果：在最初的6天剥夺期后观察到ADE，并且ADE显著增强（即，ADE的递增）。与单一浓度的15%乙醇相比，同时使用多种乙醇浓度导致基线乙醇消耗量增加近2倍。无论是否获得单一或多种浓度的乙醇，在2周剥夺期后均未立即观察到ADE。每周重复暴露于单一或多种浓度的乙醇后，观察到ADE（尽管幅度和持续时间较小）。或者，在2周的剥夺期后，每天接受15%乙醇的小鼠显示出乙醇摄入和偏好的显著降低（即，结论：短期剥夺后重复间歇性（每周）再暴露于乙醇在B6小鼠中产生了强烈的ADE。将初始剥夺长度增加至2周产生各种相反的效应，包括初始ADE的消除、每周暴露后ADE的表达和幅度减少以及每日暴露于乙醇后ADE的完全逆转。
Background: Relapse-like drinking has been studied through the expression of the alcohol deprivation effect (ADE), which is measured by a pronounced increase in ethanol preference and consumption after imposed abstinence. No studies have characterized the ADE in C57BL/6J (B6) mice. The present study examined the effects of length and number of deprivations on the expression of the ADE in B6 mice.Methods: Adult male B6 mice received 24-hour continuous access to ethanol and water for 6 weeks (baseline). Experiment 1 determined the ADE in mice receiving weekly access to 15% ethanol (i.e., exposed 1 day a week and deprived during the other 6 days) for a total of 10 weeks. Experiments 2 and 3 determined the ADE after a single 2-week deprivation period in mice receiving a single concentration of 15% ethanol or multiple concentrations of 7.5, 15, and 30% ethanol, respectively, followed by weekly access to their respective ethanol solutions for 10 weeks. Experiment 4 determined the ADE after a single 2-week deprivation period, followed by daily access to 15% ethanol. Mice never deprived of ethanol (i.e., continuous access) were used as age-matched drinking controls.Results: The ADE was observed after the initial 6-day deprivation period and was profoundly enhanced (i.e., escalation of the ADE) following weekly reexposure to 15% ethanol. Compared with a single concentration of 15% ethanol, concurrent access to multiple ethanol concentrations resulted in a near 2-fold increase in baseline ethanol consumption. Regardless of having access to single or multiple concentrations of ethanol, the ADE was not observed immediately after a 2-week deprivation period. The ADE was observed (although to a lesser magnitude and duration) following weekly reexposure to single or multiple concentrations of ethanol. Alternatively, following a 2-week deprivation period, mice receiving daily access to 15% ethanol showed a significant decrease in ethanol intake and preference (i.e., negative ADE).Conclusions: Short-term deprivations followed by repeated intermittent (weekly) reexposure to ethanol produces a robust ADE in B6 mice. Increasing the initial deprivation length to 2 weeks produces various opposing effects, including erasure of an initial ADE, diminished expression and magnitude of the ADE following weekly exposure, and complete reversal of the ADE following daily exposure to ethanol.