Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers
Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers
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DOI：
10.1002/syn.1098
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发表时间：
2001-10-01
期刊：
影响因子：
2.3
通讯作者：
Cumming, P
中科院分区：
文献类型：
--
作者：
Dagher, A;Bleicher, C;Cumming, P
包括尼古丁在内的几种滥用药物被认为是通过对中脑边缘多巴胺系统的作用来发挥其强化作用。动物和人类研究表明，长期服用成瘾药物可能会导致丘脑核中多巴胺神经传递受损。我们使用正电子发射断层扫描和D1受体配体[C-11]SCH 23390测量了11名吸烟者和18名非吸烟者的DI受体密度。其中10名吸烟者被扫描两次，一次是在整夜戒烟后，一次是在以正常速度吸烟时，以说明吸烟对D1受体结合的可能急性影响。此外，对8名对照受试者进行了两次扫描，以评估该方法的重现性。我们使用房室模型测定[C-11]SCH 23390结合潜力，这是D1受体密度的一种指标。吸烟者的戒烟和非戒烟扫描之间或对照组的两次扫描之间的结合没有差异。然而，与非吸烟者相比，吸烟者纹状体中[C-11]SCH 23390的结合潜力显著降低，在腹侧纹状体中最显著。这表明，有一个减少多巴胺D1受体密度在腹侧纹状体的吸烟者相对于非吸烟者，这意味着突触后中脑边缘多巴胺系统可能是慢性不活跃的吸烟者，无论是作为一个前因或结果的香烟成瘾。这种低多巴胺能状态可能在维持尼古丁寻求行为中起重要作用。或者，纹状体中多巴胺受体的遗传性减少可能与成瘾行为的风险增加有关。Synapse 42：48-53，2001. (C)2001 Wiley-Liss，Inc.
Several drugs of abuse, including nicotine, are thought to exert their reinforcing effects through actions on the mesolimbic dopamine system. Animal and human studies suggest that chronic administration of addictive drugs may lead to impaired dopamine neurotransmission in the nucleus accumbens. We measured DI receptor density in 11 smokers and 18 nonsmokers using positron emission tomography and the D1 receptor ligand [C-11]SCH 23390. Ten of the smokers were scanned twice, once after overnight abstinence from cigarettes, and once while smoking at their usual rate, to account for possible acute effects of cigarette smoking on D1 receptor binding. In addition, eight control subjects were scanned twice to assess the reproducibility of the method. We used compartmental modeling to measure [C-11]SCH 23390 binding potential, a measure of D1 receptor density. There were no differences in binding between abstinent and nonabstinent scans in smokers or in the two scans in controls. However, there was a significant reduction in [C-11]SCH 23390 binding potential in smokers compared to nonsmokers in the striatum, most prominently in the ventral striatum. This suggests that there is a reduction in dopamine D1 receptor density in the ventral striatum of human cigarette smokers relative to nonsmokers, which implies that the postsynaptic mesolimbic dopamine system may be chronically underactive in smokers, either as an antecedent or consequence of addiction to cigarettes. Such a hypodopaminergic state may play an important role in sustaining nicotine-seeking behavior. Alternatively, an inherited reduction in dopamine receptors in the striatum may be associated with an increased risk of addictive behavior. Synapse 42:48-53, 2001. (C) 2001 Wiley-Liss, Inc.