Aalto Sargo, Ingman Kimmo, Alakurtti Kati, Kaasinen Valtteri, Virkkala Jussi, Någren Kjell, Rinne Juha O, Scheinin Harry
1] Turku PET Centre, University of Turku, Turku, Finland [2] Department of Psychology, Åbo Akademi University, Åbo, Finland.
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
J Cereb Blood Flow Metab. 2015 Mar;35(3):424-31. doi: 10.1038/jcbfm.2014.209. Epub 2014 Dec 10.
Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
乙醇可提高实验动物伏隔核(NAcc)中的间质多巴胺(DA)浓度,但使用[(11)C]雷氯必利竞争范式的单剂量方案进行的正电子发射断层扫描(PET)研究在人类中得出了相互矛盾的结果。为了解决先前不同的研究结果,我们采用了推注加输注(B/I)方法,在单次105分钟的PET扫描期间对[(11)C]雷氯必利结合进行基线和干预定量,以研究9名健康男性受试者中乙醇诱导的DA释放情况。在PET扫描期间采用隐蔽计时,静脉输注25分钟乙醇(7.6%),导致平均血乙醇浓度达到1.3 g/L。通过自动感兴趣区分析测试基线(40 - 50分钟)和干预(60 - 85分钟)之间的差异,发现包括伏隔核在内的腹侧纹状体(VST)中[(11)C]雷氯必利结合平均下降了12.6%(P = 0.003)。此外,从乙醇输注开始到出现首个主观效应的时间间隔越短,双侧VST中的结合潜能下降幅度越大(r = 0.92,P = 0.004),并且愉悦感与尾状核(r = -0.87,P = 0.003)和壳核(r = -0.74;P = 0.02)中结合潜能值的下降有关。这些结果证实,乙醇可诱导边缘纹状体中DA快速释放,使用B/I方法在一次成像过程中就能可靠地估算出来。