Hospital of Psychiatry Muensingen and University Hospital of Psychiatry Bern, University of Bern, Bern 60, Switzerland.
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Addict Biol. 2017 Sep;22(5):1449-1458. doi: 10.1111/adb.12424. Epub 2016 Jul 11.
Investigations on the acute effects of alcohol in the human mesolimbic dopamine D /D receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D /D dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D /D receptor ligand [ F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D /D binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D /D dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D /D receptors may hint at an addiction relevant trait.
人类中脑边缘多巴胺 D /D 受体系统中酒精的急性效应研究结果相互矛盾。关于酒精对纹状体外多巴胺 D /D 受体的影响,目前尚未有研究报道。因此,我们应用正电子发射断层扫描(PET)成像技术,使用突触后多巴胺 D /D 受体配体[ F]fallypride,研究了静脉内给予酒精是否刺激纹状体外和纹状体多巴胺系统。我们测量了酒精的主观效应,并与纹状体和纹状体外 D /D 结合潜能进行了相关性分析。24 名健康的 μ 阿片受体(OPRM1)118G 等位基因携带者接受了标准化的静脉内和安慰剂酒精给药。酒精的主观效应通过视觉模拟量表进行测量。为了评估多巴胺反应,我们使用简化参考组织模型(SRTM)计算了结合潜能(BP)。此外,我们在 10 名可用代谢物校正动脉样本的受试者中计算了靶区和参照区的分布容积。在酒精状态下,未观察到纹状体和纹状体外脑区 BP 显著降低的多巴胺反应。我们发现“喜欢”酒精与纹状体外脑区 BP 呈正相关(额叶下回(IFC)(r = 0.533,p = 0.007),眶额皮质(OFC)(r = 0.416,p = 0.043)和前额叶皮质(PFC)(r = 0.625,p = 0.001))。我们的实验中,急性酒精对纹状体和纹状体外系统 D /D 多巴胺受体结合潜能的影响不显著。主观“喜欢”酒精的效应与皮质 D /D 受体呈正相关,这可能暗示着与成瘾相关的特质。