Tupala Erkki, Hall Håkan, Halonen Pirjo, Tiihonen Jari
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Kuopio, FIN-70240 Kuopio, Finland.
Synapse. 2004 Dec 1;54(3):129-37. doi: 10.1002/syn.20071.
Alcoholism has been associated with lower density of striatal dopamine (DA) D(2) receptors, but there is much less data on cortical DA D(2) receptors. We evaluated the [(125)I]epidepride binding to DA D(2) receptors in Cloninger type 1 and 2 alcoholics and controls in frontal, temporal, and anterior cingulate cortices by using human postmortem whole hemispheric autoradiography, which provides high-resolution images corresponding to positron emission tomographic (PET) studies. Type 1 alcoholics had lower and type 2 alcoholics had higher DA D(2) receptor density in all cortical areas compared to controls. Although the results did not reach statistical significance, the effect sizes were high. The DA D(2) receptor density in type 2 alcoholics decreased statistically significantly with age, and after correcting for age the binding values also fell below the level of controls. A statistically non-significant tendency towards a decrease of cortical DA D(2) receptors was seen in controls, whereas in the type 1 alcoholic group no consistent correlation or even tendency towards increase with age was observed. Our results give preliminary evidence that DA D(2) receptors in cortical areas may be lower among both groups of alcoholics, but not necessarily of same magnitude as in subcortical structures. The rapid decline of cortical DA D(2) receptors among type 2 alcoholics may have some relevance to their antisociality, because this trait tends to diminish with age. The absence of correlation or even tendency towards increase of cortical DA D(2) receptors with age seen in type 1 alcoholics may give further evidence that they have a pre-existing dopaminergic deficit. However, these results especially regarding aging effect must be considered as preliminary due to the different age-range of type 2 alcoholics compared to two other groups.
酒精中毒与纹状体多巴胺(DA)D₂受体密度降低有关,但关于皮质DA D₂受体的数据要少得多。我们通过使用人类死后全脑半球放射自显影技术,评估了克隆宁格1型和2型酒精依赖者以及对照组额叶、颞叶和前扣带回皮质中[¹²⁵I]表哌立登与DA D₂受体的结合情况,该技术可提供与正电子发射断层扫描(PET)研究相对应的高分辨率图像。与对照组相比,1型酒精依赖者在所有皮质区域的DA D₂受体密度较低,而2型酒精依赖者的DA D₂受体密度较高。尽管结果未达到统计学显著性,但效应量很大。2型酒精依赖者的DA D₂受体密度随年龄增长有统计学显著下降趋势,校正年龄后结合值也低于对照组水平。对照组中皮质DA D₂受体有统计学不显著的下降趋势,而在1型酒精依赖者组中未观察到与年龄一致的相关性甚至增加趋势。我们的结果提供了初步证据,表明两组酒精依赖者皮质区域的DA D₂受体可能较低,但不一定与皮质下结构中的程度相同。2型酒精依赖者皮质DA D₂受体的快速下降可能与其反社会行为有关,因为这种特征往往会随着年龄增长而减弱。1型酒精依赖者中未观察到皮质DA D₂受体与年龄的相关性甚至增加趋势,这可能进一步证明他们存在预先存在的多巴胺能缺陷。然而,由于2型酒精依赖者与其他两组的年龄范围不同,这些结果尤其是关于衰老效应的结果必须被视为初步的。