A PET Study of Ventral Striatum Dopamine Release Deficits

在CTNA-1期间，我们使用了高分辨率正电子发射断层扫描(PET)和D2受体 放射性示踪剂[11C]拉氯必利研究DA传递的两个参数：D2受体密度和 安非他明诱导戒酒患者腹侧纹状体突触内多巴胺释放 受试者和健康对照组发现：1)最近在所有纹状体亚区D2受体减少 戒毒酒精依赖患者与对照组的比较，2)D2下降之间的关系 所有纹状体亚区的受体和每日饮酒的严重程度，以及3)区域选择性地减少 安非他明诱导酒精依赖受试者腹侧纹状体DA释放的比较 控制。腹侧纹状体的低DA传递和纹状体D2受体的低可获得性可能是 易患酒精依赖的因素，或者也可以反映长期酒精依赖的影响 利用大脑中的奖赏回路。我们现在建议用正电子发射计算机断层扫描检查多巴胺的传递。 和[11C]拉氯普利和苯丙胺挑战+FH与-FH配对健康志愿者。这个 纹状体[11]CJraclopide结合势(BP)和特定到非特定平衡分配系数 (V3“)将被测量并在两组之间进行比较(SA1)。苯丙胺诱导的 [11 C]拉克洛必利V3“将在两组之间进行比较(SA2)。在高风险组中，我们预测 D2的减少将与饮酒的严重程度有关，这些严重程度是通过每天的消耗量来衡量的。这将是 对于-FH受试者则不是这样，这表明低D2是易损性的标志，而不是毒性 (SAS)。这项研究建立在我们目前的发现基础上，并将多巴胺能传递的研究扩展到一个很高的水平 风险人群。在酒精中毒发生之前确认高危人群中的这些变化将是第一次 在了解脆弱性的生物学基础方面迈出了一步。这可能会导致开发一种生物标记物 确定高危受试者，并可能为预防设计具体的治疗策略。

During CTNA-1 we used high resolution Positron Emission Tomography (PET) and the D2 receptor radiotracer [11 C]raclopride to study two parameters of DA transmission: D2 receptor density and amphetamine-induced intrasynaptic DA release in the ventral striatum in currently abstinent alcoholic subjects and healthy controls and found: 1) decreased D2 receptors in all striatal subregions in recently detoxified alcohol dependent patients compared to controls, 2) a relationship between the decrease in D2 receptors and the severity of daily drinking in all striatal subregions, and 3) a regionally selective decrease in amphetamine induced DA release in the ventral striatum in alcohol dependent subjects compared to controls. Low DA transmission in the ventral striatum and low striatal D2 receptors availability may both be predisposing factors to developing alcohol dependence or could alternatively reflect the effects of long term use on the reward circuitry in the brain. We now propose now to examine dopamine transmission with PET and [11 C]raclopride and the amphetamine challenge in +FH versus -FH matched healthy volunteers. The striatal [11 CJraclopride binding potential (BP) and the specific to nonspecific equilibrium partition coefficient (V3") will be measured and compared between the two groups (SA1). Amphetamine-induced reduction in [11 C]raclopride V3" will be compared between the two groups (SA2). In the high risk group we predict that decreased D2 will be related to severity of drinking measured by the amount of daily consumption. This will not be the case for -FH subjects indicating that low D2 is a marker for vulnerability rather than toxicity (SAS).This study builds on our current findings and extends the study of dopaminergic transmission to a high risk population. Confirming these alterations in at risk subjects prior to the onset of alcoholism will be a first step in understanding the biological basis of vulnerability. This could lead to developing a biomarker for identifying at risk subjects and possibly designing specific therapeutic strategies for prevention.