Increased Ethanol Self‐Administration in δ‐Opioid Receptor Knockout Mice
Increased Ethanol Self‐Administration in δ‐Opioid Receptor Knockout Mice
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DOI：
10.1111/j.1530-0277.2001.tb02344.x
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发表时间：
2001-09
期刊：
影响因子：
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通讯作者：
A. Roberts;L. Gold;I. Polis;J. McDonald;D. Filliol;B. Kieffer;G. Koob
中科院分区：
文献类型：
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作者：
A. Roberts;L. Gold;I. Polis;J. McDonald;D. Filliol;B. Kieffer;G. Koob
尽管使用了传统的药理学和相关方法，δ阿片受体在乙醇饮用中的作用仍然不清楚。几项研究的结果表明，这些受体的药理学阻断导致饮酒行为减少，但大约相同数量的报告未能观察到δ受体拮抗剂对饮酒的影响。很明显，需要其他方法来理解阿片受体参与乙醇饮用。方法采用双瓶选择实验、操作性自我给药实验和双瓶选择实验，对δ阿片受体敲除（KO）小鼠的乙醇饮酒行为进行研究。此外，由于先前显示KO小鼠相对于野生型（WT）小鼠表现出增强的焦虑样行为，因此确定了乙醇自身给药对焦虑样反应的影响。delta KO小鼠最初在第一次两瓶选择饮酒试验中没有表现出对乙醇的偏好;然而，在操作性自我给药乙醇后，在第二次两瓶选择试验中对乙醇产生了偏好。KO小鼠还显示出对乙醇的偏好超过水，并且在操作性自我给药范例中自我给药的乙醇比WT小鼠多。在该程序中自我施用的乙醇足以逆转在该菌株中观察到的先天性焦虑样反应。结论：delta KO小鼠表现出对乙醇的更大偏好，并且比WT小鼠消耗更多的乙醇，这表明delta受体活性的降低与饮酒行为的增加有关。据推测，δ受体可能会影响乙醇自我管理，至少部分通过这些受体对焦虑样行为的影响。
BACKGROUND The role of the delta-opioid receptor in ethanol drinking has remained unclear despite the use of traditional pharmacological and correlational approaches. The results of several studies suggest that pharmacological blockade of these receptors results in decreases in ethanol drinking behavior, but an approximately equal number of reports have failed to observe an effect of delta-receptor antagonism on ethanol drinking. It is clear that alternative approaches to understanding opioid-receptor involvement in ethanol drinking are needed. METHODS In this study, ethanol drinking was examined in delta-opioid receptor knockout (KO) mice by using first a two-bottle-choice test, then an operant self-administration paradigm and a second two-bottle-choice test, in that order. In addition, because KO mice were previously shown to display enhanced anxiety-like behavior relative to wild-type (WT) mice, the effect of ethanol self-administration on anxiety-like responses was determined. RESULTS delta KO mice initially showed no evidence of a preference for ethanol in the first two-bottle-choice drinking test; however, after an experience of operant self-administration of ethanol, a preference for ethanol developed in the second two-bottle-choice test. KO mice also showed a preference for ethanol over water and self-administered more ethanol than WT mice in the operant self-administration paradigm. The ethanol self-administered in this procedure was sufficient to reverse the innate anxiety-like response observed in this strain. CONCLUSIONS delta KO mice showed a greater preference for ethanol and consumed more ethanol than their WT counterparts, suggesting that a decrease in delta-receptor activity is associated with increased ethanol-drinking behavior. It is hypothesized that delta receptors may influence ethanol self-administration at least partly through an effect of these receptors on anxiety-like behavior.