Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum
Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum
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DOI：
10.1016/j.biopsych.2005.04.044
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发表时间：
2005-11-15
影响因子：
10.6
通讯作者：
Abi-Dargham, A
中科院分区：
文献类型：
--
作者：
Martinez, D;Gil, R;Abi-Dargham, A
背景：多巴胺2型受体（D-2）和中脑边缘多巴胺传递的减少使动物易于饮酒。本研究测量了D-2受体和多巴胺的传输在人类酒精依赖（AD）的主题，使用正电子发射断层扫描（PET）和[C-11]raclopride.Methods：15 AD和15名健康对照（HC）受试者进行扫描之前和之后的精神兴奋剂苯丙胺（安非他明3毫克/公斤静脉注射）。基线D-2受体可用性的结果指标是结合势（BP）和平衡分配系数（V-3”）。苯丙胺诱导的[C-11]雷氯必利位移测量为两次扫描之间V-3“的差异。结果：与HC相比，AD受试者的[C-11]雷氯必利BP在边缘纹状体中显著降低16.6%，在联合纹状体中显著降低19.2%，在感觉运动纹状体中显著降低21.3%。酒精依赖受试者显示边缘层安非他明诱导的多巴胺释放减弱：AD受试者[C-11]雷氯必利置换为-5.2% +/- 3.6%，HC受试者为-13.0% +/- 8.8%。然而，在相关性中没有观察到[C-11]雷氯必利置换的显著差异。（AD受试者为-4.6% +/- 5.8%，HC为-6.7 +/- 5.4%）和感觉运动（AD受试者为-12.3% +/- 7.3%，HC为-13.7% +/- 7.5%）两组之间纹状体的细分。酒精依赖与D-2受体在每个straital细分减少，而安非他明诱导的多巴胺释放减少边缘纹状体。
Background: A decrease in dopamine type 2 receptors (D-2) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D-2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [C-11]raclopride.Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challene (amphetamine 3 mg/kg intravenous). The outcome measures for baseline D-2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V-3 ''). Amphetamine-induced [C-11]raclopride displacement was measured as the difference in V-3 '' between the two scans.Results: [C-11]raclopride BP was signifcantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamine-induced dopamine release in the limbic straitum: [C-11]raclopride displacement was -5.2% +/- 3.6% in AD subjects compared with -13.0% +/- 8.8% in HC. However, no significant difference in [C-11]raclopride displacement was seen in the associative (-4.6% +/- 5.8% in AD subjects vs. -6.7 +/- 5.4% in HC) and sensorimotor (-12.3% +/- 7.3% in AD subjects vs. -13.7% +/- 7.5% in HC) subdivisions of the striatum between the two groups.Conclusions: Alcohol dependence was associated with a decrease in D-2 receptors in each straital subdivision, whereas amphetamine-induced dopamine release was reduced in the limbic striatum only.