The Influence of Selection for Ethanol Withdrawal Severity on Traits Associated With Ethanol Self-Administration and Reinforcement
The Influence of Selection for Ethanol Withdrawal Severity on Traits Associated With Ethanol Self-Administration and Reinforcement
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DOI：
10.1111/j.1530-0277.2010.01348.x
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发表时间：
2011-02-01
影响因子：
3.2
通讯作者：
Finn, Deborah A.
中科院分区：
文献类型：
--
作者：
Ford, Matthew M.;Fretwell, Andrea M.;Finn, Deborah A.
背景：一些荟萃分析表明，乙醇偏好饮酒与乙醇戒断严重程度之间存在负相关的遗传关系，但有限的工作已经在1种遗传动物模型中表征了乙醇消耗，分别选择了严重或轻度乙醇戒断的戒断发作倾向（WSP）和抗性（WSR）小鼠系。方法：我们确定了在以下方面是否存在系差异：(i)在蔗糖消退期间和不同的强化时间表下，乙醇的操作性自我给药，随后对条件提示的反应消失和恢复；（ii）在家笼中饮用加糖乙醇和酒精剥夺效应（ADE）的发展。结果：在固定比例(FR)-4计划下，当乙醇逐渐消失到蔗糖溶液中时，戒断癫痫倾向-1小鼠比WSR-1小鼠消耗更多的乙醇，但随着蔗糖逐渐消失，产生10% v/v的纯乙醇溶液，这种线差消失。相比之下，WSR-1小鼠比WSP-1小鼠消耗更多的乙醇，当一个时间表被强加，程序性分离食欲和完善行为。在两条线都达到消退标准后，在口服乙醇启动、光提示和两种线索的组合后，对恢复情况进行了连续评估。光提示在WSP-1小鼠中产生最大的反应恢复，而组合提示在WSR-1小鼠中产生最大的反应恢复。在1个月的时间里，加糖乙醇溶液的家庭笼消耗没有直线差异。禁欲2周后，两组均未发生ADE。结论：尽管在WSP-1和WSR-1小鼠之间发现了乙醇自我给药和恢复的一些系差异，但缺乏一致的差异表明，这些行为背后的基因并不一定与控制戒断严重程度的基因重叠。
Background:Several meta-analyses indicate that there is an inverse genetic correlation between ethanol preference drinking and ethanol withdrawal severity, but limited work has characterized ethanol consumption in 1 genetic animal model, the Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mouse lines selected for severe or mild ethanol withdrawal, respectively.Methods:We determined whether line differences existed in: (i) operant self-administration of ethanol during sucrose fading and under different schedules of reinforcement, followed by extinction and reinstatement of responding with conditioned cues and (ii) home cage drinking of sweetened ethanol and the development of an alcohol deprivation effect (ADE).Results:Withdrawal Seizure-Prone-1 mice consumed more ethanol than WSR-1 mice under a fixed ratio (FR)-4 schedule as ethanol was faded into the sucrose solution, but this line difference dissipated as the sucrose was faded out to yield an unadulterated 10% v/v ethanol solution. In contrast, WSR-1 mice consumed more ethanol than WSP-1 mice when a schedule was imposed that procedurally separated appetitive and consummatory behaviors. After both lines achieved the extinction criterion, reinstatement was serially evaluated following oral ethanol priming, light cue presentation, and a combination of the 2 cues. The light cue produced maximal reinstatement of responding in WSP-1 mice, whereas the combined cue was required to produce maximal reinstatement of responding in WSR-1 mice. There was no line difference in the home cage consumption of a sweetened ethanol solution over a period of 1 month. Following a 2-week period of abstinence, neither line developed an ADE.Conclusions:Although some line differences in ethanol self-administration and reinstatement were identified between WSP-1 and WSR-1 mice, the absence of consistent divergence suggests that the genes underlying these behaviors do not reliably overlap with those that govern withdrawal severity.