Imaging D3 receptors in alcoholism.

酒精滥用，特别是依赖性酒精使用，使英国社会每年损失约200亿英镑，NHS每年损失17亿英镑。据估计，英国有110万人依赖酒精。通常治疗包括心理社会方法，但药物越来越多地被认为在支持任何变化或进展方面发挥重要作用。增加关于酒精或成瘾如何影响大脑的知识？的化学导致了新的药物成为可用。多巴胺是大脑中一种特殊的化学系统，很长一段时间以来人们都知道它参与了调解？喜欢喝酒吗还参与了酗酒吗在那些已经成为依赖酒精（即酒精）。在多巴胺能系统内，多巴胺D3受体（DRD 3）最近已在动物模型中显示在提示或应激诱导的复发中起作用，此外，慢性酒精暴露可增加DRD 3水平。因此，阻断DRD 3可能在减少复发的常见原因方面具有临床益处。看到他们喝酒或压力的暗示或提醒。这项研究的目的是首次测量活体人脑中的DRD 3水平。我们正在使用一种名为正电子发射断层扫描（PET）的专门脑成像技术，该技术涉及使用示踪剂（称为11 C-PHNO），该示踪剂标记整个大脑中的DRD 3受体，包括与成瘾有关的关键区域。由于这种示踪剂也标记另一种类型的多巴胺受体（DRD 2），第二次扫描将在用称为DRD 3拮抗剂的药物阻断所有DRD 3后进行。两次扫描之间的差异将代表大脑中的DRD 3水平。由于DRD 3在介导线索诱导的复发中显得很重要，我们还将使用另一种脑成像技术，功能性磁共振成像（fMRI）来测量大脑的活动，因为这个人正在寻找酒精相关的线索，以及当他们期待不同类型的？奖励？钱然后，我们将能够研究在这些经历中DRD 3水平和大脑活动之间的关系。由于PET示踪剂和DRD 3拮抗剂的可用性，我们现在只能进行这项研究。这项研究将为我们提供有关DRD 3的重要信息，以帮助了解它在人类酒精中毒中的作用。在此基础上，进一步的研究将调查DRD 3系统在其他成瘾，如阿片类药物，赌博，为未来的治疗方法提供信息。

Alcohol misuse, especially dependent alcohol use, costs UK society around #20bn/yr and the NHS #1.7bn/yr. In the UK it is estimated that there are 1.1 million people dependent on alcohol. Typically treatment consists of psychosocial approaches however medication is increasingly recognised to play an important role to support any changes or progress made. Increasing knowledge about how alcohol or addiction can affect the brain?s chemistry has led to new medications becoming available. One particular chemical system in the brain, dopamine has been known for a long time to be involved in mediating ?alcohol-liking? but is also involved in ?alcohol-seeking? in those that have become dependent on alcohol (i.e. alcoholic). Within the dopaminergic system, the dopamine D3 receptor (DRD3), has been recently shown in animal models to play a role in cue or stress induced relapse and in addition chronic alcohol exposure can increase DRD3 levels. Therefore blocking the DRD3 is likely to be of clinical benefit in reducing the commonly cited reasons for relapsing ? seeing a cue or reminder of their drinking or stress. The aim of this proposal is to measure for the first time DRD3 levels in the living human brain. We are using a specialised brain imaging technique called positron emission tomography (PET) which involves using a tracer (called 11C-PHNO) which labels the DRD3 receptor throughout the brain including in key areas involved in addiction. Since this tracer also labels another type of dopamine receptor (DRD2) a second scan will take place after blocking all DRD3 with a drug, called a DRD3 antagonist. The difference between the two scans will represent DRD3 levels in the brain. Since the DRD3 appears important in mediating cue-induced relapse we will also measure activity in the brain using another brain imaging technique, functional magnetic resonance imaging (fMRI), as the person is looking at alcohol-related cues as well as when they are anticipating a different type of ?reward?, money. We will then be able to investigate the relationship between DRD3 levels and brain activity during these experiences. We are only able to conduct this study now due to the availability of the PET tracer and DRD3 antagonist. This study will give us important information about DRD3 to help understand its role in human alcoholism. Building on this, further studies will investigate the DRD3 system in other addictions eg opiate, gambling to inform future therapeutic approaches.