Imaging D3 receptors in alcoholism.

酒精中毒中 D3 受体的成像。

• 批准号: G0802723/1
• 负责人: Anne Lingford Hughes
• 金额: $ 27.47万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802723%2F1
• 关键词: Imaging; D3; receptors; alcoholism.

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.

滥用酒精，尤其是依赖酒精的使用，每年给英国社会造成约 200 亿美元的损失，为 NHS 造成每年 17 亿美元的损失。在英国，估计有 110 万人依赖酒精。通常治疗包括心理社会方法，但人们越来越认识到药物在支持任何改变或进展方面发挥着重要作用。随着人们对酒精或成瘾如何影响大脑化学物质的了解不断增加，新的药物也随之出现。多巴胺是大脑中一种特殊的化学系统，长期以来人们都知道它与调节“酒精喜好”有关。但也参与了“寻求酒精”？对于那些已经变得依赖酒精的人（即酗酒者）。最近在动物模型中显示，在多巴胺能系统中，多巴胺 D3 受体 (DRD3) 在提示或压力诱导的复发中发挥作用，此外，长期接触酒精会增加 DRD3 水平。因此，阻断 DRD3 可能对减少常见的复发原因具有临床益处？看到他们饮酒或压力的暗示或提醒。该提案的目的是首次测量活人大脑中 DRD3 的水平。我们正在使用一种称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 11C-PHNO）来标记整个大脑（包括与成瘾相关的关键区域）的 DRD3 受体。由于该示踪剂还标记了另一种类型的多巴胺受体 (DRD2)，因此在使用称为 DRD3 拮抗剂的药物阻断所有 DRD3 后将进行第二次扫描。两次扫描之间的差异将代表大脑中 DRD3 的水平。由于 DRD3 在调节线索诱发的复发中似乎很重要，因此我们还将使用另一种脑成像技术，即功能性磁共振成像 (fMRI) 来测量大脑中的活动，因为人们正在观察与酒精相关的线索以及当他们预期时另一种“奖励”，金钱。然后我们将能够研究这些经历期间 DRD3 水平与大脑活动之间的关系。由于 PET 示踪剂和 DRD3 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 DRD3 的重要信息，以帮助我们了解它在人类酗酒中的作用。在此基础上，进一步的研究将调查其他成瘾（例如鸦片、赌博）中的 DRD3 系统，为未来的治疗方法提供信息。