Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
J Neurosci. 2013 Jun 12;33(24):10027-36. doi: 10.1523/JNEUROSCI.0695-13.2013.
Functional polymorphisms in the dopamine transporter gene (DAT1 or SLC6A3) modulate responsiveness to salient stimuli, such that carriers of one 9R-allele of DAT1 (compared with homozygote carriers of the 10R-allele) show heightened reactivity to drug-related reinforcement in addiction. Here, using multimodal neuroimaging and behavioral dependent variables in 73 human cocaine-addicted individuals and 47 healthy controls, we hypothesized and found that cocaine-addicted carriers of a 9R-allele exhibited higher responses to drug cues, but only among individuals who had used cocaine within 72 h of the study as verified by positive cocaine urine screens (a state characterized by intense craving). Importantly, this responsiveness to drug cues was reliably preserved across multimodal imaging and behavioral probes: psychophysiological event-related potentials, self-report, simulated cocaine choice, and fMRI. Because drug cues contribute to relapse, our results identify the DAT1R 9R-allele as a vulnerability allele for relapse especially during early abstinence (e.g., detoxification).
多巴胺转运体基因（DAT1 或 SLC6A3）中的功能多态性调节对显著刺激的反应性，使得 DAT1 的一个 9R-等位基因携带者（与 10R-等位基因的纯合子携带者相比）对成瘾中与药物相关的强化表现出更高的反应性。在这里，我们使用多模态神经影像学和行为依赖变量，在 73 名可卡因成瘾个体和 47 名健康对照者中进行了假设和发现，可卡因成瘾的 9R-等位基因携带者对药物线索表现出更高的反应，但仅在研究前 72 小时内通过阳性可卡因尿液筛查（一种强烈渴望的状态）确认为使用过可卡因的个体中。重要的是，这种对药物线索的反应在多模态影像学和行为探针中可靠地保持一致：心理生理事件相关电位、自我报告、模拟可卡因选择和 fMRI。由于药物线索会导致复发，我们的研究结果确定 DAT1R 9R-等位基因是复发的易感性等位基因，尤其是在早期戒断期间（例如，戒毒）。
