Dopamine receptors and transporters in the brain reward circuits of type 1 and 2 alcoholics measured with human whole hemisphere autoradiography
Dopamine receptors and transporters in the brain reward circuits of type 1 and 2 alcoholics measured with human whole hemisphere autoradiography
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DOI：
10.1016/s1053-8119(03)00060-0
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发表时间：
2003-05-01
期刊：
影响因子：
5.7
通讯作者：
Tiihonen, J
中科院分区：
文献类型：
--
作者：
Tupala, E;Hall, H;Tiihonen, J
多巴胺系统在大脑奖赏机制和药物滥用发展中的作用已得到充分证实，伏隔核是介导这些作用的关键结构。一些关于酗酒的研究表明多巴胺能神经传递缺陷和多巴胺受体密度改变。然而，目前尚不清楚药物滥用相关的多巴胺能缺陷是否与某种受体亚型特异性相关。本研究的目的是比较伏隔核、杏仁核和黑质中多巴胺 D-1、D-2 和 D-3 受体的假定变化。在酗酒者和控制者之间。我们通过使用死后人类整个半球放射自显影技术，研究了 9 名 1 型酗酒者、8 名 2 型酗酒者和 10 名健康对照者大脑中多巴胺 D-1 和 D-3 受体的密度。所有研究组中多巴胺 D-1 和 D-3 受体的平均密度处于相同水平。结合我们之前的结果，我们的数据表明，在 I 型酗酒者中，伏核和多巴胺 D-2 中的多巴胺转运蛋白较低，但伏核和杏仁核中的 D-1 或 D-3 受体则较低。此外，2 型酗酒者中所有这些多巴胺结合位点的密度都处于健康对照的水平。结果表明，较低的多巴胺受体密度是 D-2 受体和 I 型酒精中毒所特有的，这支持了 Cloninger 的两种酒精亚型的神经遗传学模型，并表明在研究与多巴胺能活性相关的问题时，对这些亚型分别进行分类的重要性。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
The role of the dopamine system in brain reward mechanisms and development of substance abuse is well-established with nucleus accumbens as a key structure in mediating these effects. Several studies on alcoholism have indicated defects in dopaminergic neurotransmission and alterations in dopamine receptor densities. However, it has remained unclear if the substance abuse-related dopaminergic defect is specifically associated with a certain receptor subtype. The aim of this study was to compare putative alterations of dopamine D-1 D-2 and D-3 receptors in nucleus accumbens, amygdala, and substantia nigra. among alcoholics and controls. We studied the densities of dopamine D-1 and D-3 receptors in brains of 9 type 1 alcoholics, 8 type 2 alcoholics, and 10 healthy controls by using postmortem human whole hemisphere autoradiography. The mean densities of dopamine D-1 and D-3 receptors were at the same level in all study groups. Combining these with our previous results, our data suggest that among type I alcoholics dopamine transporters are lower in nucleus accumbens and dopamine D-2, but not D-1 or D-3 receptors in nucleus accumbens and amygdala. Further, the densities of all these dopamine-binding sites among type 2 alcoholics are at the level of healthy controls. The results suggest that lower dopamine receptor density is specific for D-2 receptor and for type I alcoholism, which supports Cloninger's neurogenetic model of two alcoholic subtypes, and indicates the importance of classifying these subgroups separately when issues related to dopaminergic activity are studied. (C) 2003 Elsevier Science (USA). All rights reserved.