A PET Study of Ventral Striatum Dopamine Release Deficits

在CTNA-1期间，我们使用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]雷氯必利研究DA传递的两个参数：D2受体密度和 苯丙胺诱导的戒酒者腹侧纹状体突触内DA释放 结果发现：1）D_2受体在纹状体各亚区均降低， 与对照组相比，脱毒酒精依赖患者，2）D2 受体和每日饮酒的严重程度在所有纹状体亚区，和3）区域选择性减少， 安非他明诱导的DA释放在腹侧纹状体酒精依赖的受试者相比， 对照腹侧纹状体中的低DA传递和低纹状体D2受体可用性可能都是 诱发因素发展酒精依赖或可能反映长期的影响， 大脑中的奖赏回路。我们现在建议用正电子发射断层扫描来检查多巴胺的传递 和[11 C]雷氯必利和安非他明的挑战，在+FH与-FH匹配的健康志愿者。的 纹状体[11 C]雷氯必利结合电位（BP）和特异性与非特异性平衡分配系数 (V3"）进行测量并比较两组之间的差异（SA1）。安非他明引起的 [11将在两组之间比较[C]雷氯必利V3 "（SA2）。在高危人群中，我们预测， 降低的D2将与通过每日消耗量测量的饮酒严重程度相关。这将 - FH受试者的情况并非如此，表明低D2是脆弱性而非毒性的标志物 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高水平， 风险人群。在酒精中毒发作之前证实这些风险受试者的变化将是第一次。 了解脆弱性的生物学基础。这可能会导致开发一种生物标志物， 确定有风险的受试者，并可能设计具体的预防治疗策略。

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.