Yoder Karmen K, Constantinescu Cristian C, Kareken David A, Normandin Marc D, Cheng Tee-Ean, O'Connor Sean J, Morris Evan D
Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res. 2007 Jun;31(6):965-73. doi: 10.1111/j.1530-0277.2007.00390.x. Epub 2007 Apr 11.
A dopaminergic response to alcohol in humans has not been demonstrated consistently with positron emission tomography (PET). We hypothesized that the effect of alcohol on striatal dopamine (DA) release may be anatomically heterogeneous between subjects. Our approach was to identify voxels that exhibited alcohol-induced DA responses within the striatum, and to determine the relationships between DA responses and alcohol-related behavior.
A novel method was developed to examine the anatomic extent and magnitude of striatal DA responses to alcohol across subjects. Thirteen healthy control subjects underwent 2 PET scans with [11C]raclopride (1 at baseline, 1 with an i.v. alcohol infusion to a target breath alcohol concentration of either 60 or 80 mg%). Parametric images of striatal binding potential (BP) were used to create maps of change in BP (deltaBP, an index of changes in DA levels). The anatomic extent and magnitude of DA responses were determined with voxel extraction methods. Subjective responses ("High," "Intoxication") to the alcohol infusion and behavioral data from the 90-day time-line follow back were assessed for relationships with DA responses to alcohol.
A voxel-wise t-test between baseline and alcohol BP images did not show any differences in D2/D3 receptor availability between the conditions. Data from the striatal deltaBP maps nevertheless showed that the anatomic extent and magnitude of alcohol-induced DA release in the striatum are correlated with subjective responses to alcohol.
The heterogeneity of dopaminergic responses to alcohol across subjects may be a reason for the lack of reports demonstrating DA involvement in alcohol-related behaviors. By allowing for different spatial patterns of DA release within each subject's striata, we showed correlations between alcohol-induced DA release in the striata and behavioral outcomes related to alcohol.
正电子发射断层扫描（PET）尚未始终如一地证实人类对酒精存在多巴胺能反应。我们推测，酒精对纹状体多巴胺（DA）释放的影响在个体之间可能存在解剖学上的异质性。我们的方法是识别纹状体内表现出酒精诱导的DA反应的体素，并确定DA反应与酒精相关行为之间的关系。
开发了一种新方法来检查跨个体纹状体对酒精的DA反应的解剖范围和幅度。13名健康对照受试者接受了两次使用[11C]雷氯必利的PET扫描（一次在基线时，一次静脉输注酒精使目标呼气酒精浓度达到60或80mg%）。纹状体结合电位（BP）的参数图像用于创建BP变化图（deltaBP，DA水平变化的指标）。使用体素提取方法确定DA反应的解剖范围和幅度。评估对酒精输注的主观反应（“兴奋”、“陶醉”）以及来自90天时间线随访的行为数据与对酒精的DA反应之间的关系。
基线和酒精BP图像之间的体素水平t检验未显示不同条件下D2/D3受体可用性存在任何差异。然而，来自纹状体deltaBP图的数据表明，纹状体中酒精诱导的DA释放的解剖范围和幅度与对酒精的主观反应相关。
跨个体对酒精的多巴胺能反应的异质性可能是缺乏报告证明DA参与酒精相关行为的原因。通过考虑每个个体纹状体内DA释放的不同空间模式，我们显示了纹状体内酒精诱导的DA释放与酒精相关行为结果之间的相关性。
