Imaging D3 receptors in alcoholism.

酒精滥用，尤其是依赖酒精的使用，每年给英国社会造成约200亿英镑的损失，给英国国民健康保险制度造成每年17亿英镑的损失。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，然而，人们越来越认识到，药物在支持所取得的任何改变或进展方面发挥着重要作用。对酒精或成瘾如何影响大脑的了解越来越多？S化学导致了新药的问世。多巴胺是大脑中一种特殊的化学系统，很长一段时间以来，人们一直知道它参与调节饮酒？但也参与了？酗酒？在那些已经对酒精产生依赖的人(即酗酒者)中。在多巴胺能系统中，多巴胺D3受体(DRD3)最近在动物模型中被证明在线索或应激诱导的复发中发挥作用，此外，长期酒精暴露可以增加DRD3的水平。因此，阻断DRD3可能在临床上有益于减少通常被引用的复发原因？看到饮酒或压力的提示或提醒。这项提议的目的是首次测量活着的人脑中的DRD3水平。我们正在使用一种名为正电子发射断层扫描(PET)的专门大脑成像技术，它涉及到使用一种示踪剂(称为11C-PHNO)来标记整个大脑中的DRD3受体，包括涉及成瘾的关键区域。由于这种示踪剂还标记了另一种类型的多巴胺受体(DRD2)，因此在用一种名为DRD3拮抗剂的药物阻断所有DRD3之后，将进行第二次扫描。这两次扫描之间的差异将代表大脑中DRD3的水平。由于DRD3似乎在调节线索诱导的复发方面很重要，我们还将使用另一种脑成像技术--功能磁共振成像(FMRI)来测量大脑的活动，当人们看到与酒精相关的线索时，以及当他们期待不同类型的奖励？金钱时。然后，我们将能够在这些经历中调查DRD3水平和大脑活动之间的关系。由于PET示踪剂和DRD3拮抗剂的存在，我们现在只能进行这项研究。这项研究将为我们提供有关DRD3的重要信息，以帮助我们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其他成瘾的DRD3系统，如鸦片、赌博，以提供未来的治疗方法。

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.