Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2/D3 dopamine system
Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2/D3 dopamine system
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DOI：
10.1111/adb.12424
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发表时间：
2017-09-01
影响因子：
3.4
通讯作者：
Schreckenberger，Mathias
中科院分区：
文献类型：
--
作者：
Pfeifer，Philippe;Tuescher，Oliver;Schreckenberger，Mathias
关于酒精对人类中脑边缘多巴胺D2/ d3受体系统的急性影响的研究产生了相互矛盾的结果。关于酒精对胃外D2/ d3多巴胺受体的影响，目前尚无研究报道。因此，我们使用突触后多巴胺D2/ d3受体配体进行PET成像[18F]，以解决静脉注射酒精是否刺激纹状体和纹状体外多巴胺系统的问题。我们测量了酒精的主观影响，并对纹状体和纹状体外D2/ d3结合电位进行了相关分析。24名健康男性μ阿片受体（OPRM1）118G等位基因携带者接受了标准化静脉注射和安慰剂酒精治疗。用视觉模拟量表测量酒精的主观影响。为了评估多巴胺反应，我们使用简化参考组织模型（SRTM）计算结合电位（BPND）。此外，我们计算了代谢物校正动脉样本在10个受试者中的分布体积（目标和参考区域）。在酒精条件下，纹状体和纹状体外脑区没有观察到显著的多巴胺反应，即bpnd的减少。我们发现，“喜欢”酒精与BPNDin在纹状体外脑区（额下叶皮质（IFC） （r= 0.533,p= 0.007）、眶额皮质（OFC） （r= 0.416,p= 0.043）和前额皮质（PFC） （r= 0.625,p= 0.001））呈正相关。急性酒精对纹状体和纹外系统D2/ d3多巴胺受体结合电位的影响不显著。“喜欢”酒精的主观效应与皮质D2/ d3受体的正相关可能暗示了一种与成瘾相关的特征。
Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2/D3receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2/D3dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2/D3receptor ligand [18F]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 D2/D3binding 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 (BPND) 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 BPNDwas observed in striatal and extrastriatal brain regions. We found a positive correlation for ‘liking’ alcohol and the BPNDin 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 D2/D3dopamine 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 D2/D3receptors may hint at an addiction relevant trait.