Boileau Isabelle, Assaad Jean-Marc, Pihl Robert O, Benkelfat Chawki, Leyton Marco, Diksic Mirko, Tremblay Richard E, Dagher Alain
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montréal, Quebec, Canada H3A 2B4.
Synapse. 2003 Sep 15;49(4):226-31. doi: 10.1002/syn.10226.
Microdialysis experiments in rodents indicate that ethanol promotes dopamine release predominantly in the nucleus accumbens, a phenomenon that is implicated in the reinforcing effects of drugs of abuse. The aim of the present study was to test the hypothesis in humans that an oral dose of ethanol would lead to dopamine release in the ventral striatum, including the nucleus accumbens. Six healthy subjects underwent two [(11)C]raclopride PET scans following either alcohol (1 ml/kg) in orange juice or orange juice alone. Subjective mood changes, heart rate, and blood-alcohol levels were monitored throughout the procedure. Personality traits were evaluated using the tridimensional personality questionnaire. PET images were co-registered with MRI and transformed into stereotaxic space. Statistical parametric maps of [(11)C]raclopride binding potential change were generated. There was a significant reduction in [(11)C]raclopride binding potential bilaterally in the ventral striatum/nucleus accumbens in the alcohol condition compared to the orange juice condition, indicative of increased extracellular dopamine. Moreover, the magnitude of the change in [(11)C]raclopride binding correlated with the alcohol-induced increase in heart rate, which is thought to be a marker of the psychostimulant effects of the drug, and with the personality dimension of impulsiveness. The present study is the first report that, in humans, alcohol promotes dopamine release in the brain, with a preferential effect in the ventral striatum. These findings support the hypothesis that mesolimbic dopamine activation is a common property of abused substances, possibly mediating their reinforcing effects.
对啮齿动物进行的微透析实验表明,乙醇主要促进伏隔核中的多巴胺释放,这一现象与滥用药物的强化作用有关。本研究的目的是在人类中验证以下假设:口服一定剂量的乙醇会导致腹侧纹状体(包括伏隔核)中的多巴胺释放。六名健康受试者在饮用橙汁中的酒精(1毫升/千克)或仅饮用橙汁后,接受了两次[(11)C]雷氯必利正电子发射断层扫描(PET)。在整个过程中监测主观情绪变化、心率和血液酒精水平。使用三维人格问卷评估人格特质。PET图像与磁共振成像(MRI)进行配准,并转换成立体定向空间。生成了[(11)C]雷氯必利结合潜能变化的统计参数图。与饮用橙汁的情况相比,在饮用酒精的情况下,腹侧纹状体/伏隔核两侧的[(11)C]雷氯必利结合潜能显著降低,表明细胞外多巴胺增加。此外,[(11)C]雷氯必利结合的变化幅度与酒精引起的心率增加相关,心率增加被认为是该药物精神刺激作用的一个标志,并且与冲动性的人格维度相关。本研究是首份报告表明,在人类中,酒精会促进大脑中的多巴胺释放,对腹侧纹状体有优先作用。这些发现支持了以下假设:中脑边缘多巴胺激活是滥用物质的共同特性,可能介导它们的强化作用。