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采用人类全脑放射自显影术测量1型和2型酒精中毒者大脑皮层多巴胺D(1)受体。

Cortical dopamine D(1) receptors in type 1 and type 2 alcoholics measured with human whole hemisphere autoradiography.

作者信息

Tupala Erkki, Tiihonen Jari

机构信息

Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Kuopio, Finland.

出版信息

Psychiatry Res. 2008 Jan 15;162(1):1-9. doi: 10.1016/j.pscychresns.2006.08.007. Epub 2007 Dec 11.

Abstract

A large body of evidence indicates the importance of dopamine (DA) activation for ethanol reinforcement, and animal models of alcoholism have implied the involvement of DA D(1) receptors in this context. We studied cortical DA D(1) receptors in nine type 1 alcoholics (late-onset, binge-drinker), eight type 2 alcoholics (early-onset, antisocial) and 10 controls by using [(3)H]SCH23390 as a radioligand in postmortem human whole hemisphere autoradiography. We also evaluated correlations of DA D(1) receptors between the cortical and subcortical areas and between cortical DA transporters and DA D(2) and D(3) receptors by comparing the present results to our earlier studies. On the average, type 2 alcoholics were younger and had more violent causes of death than type 1 alcoholics and controls. There were no statistically significant differences between the groups, suggesting that cortical DA D(1) receptors do not play a major role in alcoholism. However, among type 2 alcoholics, the binding was consistently lower (8.6%-22.3%) than among controls, and the effect sizes showed a large effect in the anterior cingulate (0.90) and frontal (0.87) cortices. Interestingly, among type 2 alcoholics, the correlation of DA D(1) receptors between two ventral midbrain structures (substantia nigra and amygdala) and anterior cingulate cortex was significantly negative, whereas in the type 1 alcoholics and controls, the correlations were significantly positive.

摘要

大量证据表明多巴胺(DA)激活对乙醇强化具有重要意义,并且酒精中毒的动物模型表明DA D(1)受体参与了这一过程。我们使用[³H]SCH23390作为放射性配体,通过死后人类全脑半球放射自显影术,研究了9名1型酗酒者(迟发性、暴饮者)、8名2型酗酒者(早发性、反社会型)和10名对照者的皮质DA D(1)受体。我们还通过将当前结果与我们早期的研究进行比较,评估了皮质和皮质下区域之间以及皮质DA转运体与DA D(2)和D(3)受体之间DA D(1)受体的相关性。平均而言,2型酗酒者比1型酗酒者和对照者更年轻,且有更多暴力致死原因。各组之间没有统计学上的显著差异,这表明皮质DA D(1)受体在酒精中毒中不发挥主要作用。然而,在2型酗酒者中,结合始终低于对照组(8.6%-22.3%),效应大小在前扣带回(0.90)和额叶(0.87)皮质显示出较大影响。有趣的是,在2型酗酒者中,两个腹侧中脑结构(黑质和杏仁核)与前扣带回皮质之间的DA D(1)受体相关性显著为负,而在1型酗酒者和对照者中,相关性显著为正。

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