Dopamine D4 receptors in psychostimulant addiction.
Dopamine D4 receptors in psychostimulant addiction.
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DOI：
10.1016/b978-0-12-420118-7.00008-1
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Le Foll, Bernard
中科院分区：
文献类型：
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作者：
Di Ciano, Patricia;Grandy, David K;Le Foll, Bernard
自从20世纪90年代克隆D4受体以来，鉴于多巴胺在成瘾中的重要性，人们对该受体在药物成瘾中的作用的兴趣一直在增加。像D3受体一样，D4受体在大脑中的分布有限，这表明它可能在药物滥用中起着独特的作用。然而，与D3受体相比，很少有研究评估D4受体的重要性。这可能部分是由于相对缺乏对D4受体有选择性的化合物；早期研究主要是在缺乏D4受体的小鼠中进行的。在这篇综述中，我们总结了关于D4受体结构和定位的文献，然后回顾了D4基因敲除小鼠的数据，这些数据使用了与理解兴奋剂使用相关的行为模型。接下来，我们介绍了最近使用选择性D4激动剂和拮抗剂以及药物寻找和服用的动物模型进行的药理学研究的证据。这里总结的数据表明D4受体在兴奋剂使用复发中的作用。因此，基于D4受体拮抗剂的治疗可能是治疗尼古丁、可卡因和安非他明复发的有效方法。
Since the cloning of the D4 receptor in the 1990s, interest has been building in the role of this receptor in drug addiction, given the importance of dopamine in addiction. Like the D3 receptor, the D4 receptor has limited distribution within the brain suggesting it may have a unique role in drug abuse. However, compared to the D3 receptor, few studies have evaluated the importance of the D4 receptor. This may be due, in part, to the relative lack of compounds selective for the D4 receptor; the early studies were mainly conducted in mice lacking the D4 receptor. In this review, we summarize the literature on the structure and localization of the D4 receptor before reviewing the data from D4 knockout mice that used behavioral models relevant to the understanding of stimulant use. Next, we present evidence from more recent pharmacological studies using selective D4 agonists and antagonists and animal models of drug seeking and taking. The data summarized here suggest a role for D4 receptors in relapse to stimulant use. Therefore, treatments based on antagonism of the D4 receptor may be useful treatments for relapse to nicotine, cocaine and amphetamine use.