Duaux E, Gorwood P, Griffon N, Bourdel M C, Sautel F, Sokoloff P, Schwartz J C, Ades J, Lôo H, Poirier M F
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Université René Descartes, Hôpital Sainte-Anne, Paris, France.
Mol Psychiatry. 1998 Jul;3(4):333-6. doi: 10.1038/sj.mp.4000409.
Anatomical, pharmacological and human post-mortem studies suggest the dopamine D3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zückerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).
解剖学、药理学及人体尸检研究表明，多巴胺D3受体（DRD3）基因是药物依赖的一个候选基因。因此，我们对DRD3基因的Bal I多态性进行了关联研究，研究对象包括54名阿片类成瘾者和70名对照者。阿片类成瘾者的寻求刺激得分（采用祖克曼量表）高于对照者（P = 0.001），尤其是其中一个亚组（70%）得分明显更高，超过了24分。整体而言，患者与对照者在基因型上没有显著差异。然而，寻求刺激得分高于24分的患者中，两个等位基因均为纯合子的情况比寻求刺激得分低于24分的患者（P = 0.038）或对照者（P = 0.034）更为常见。尽管这些结果是在一个规模有限的样本中获得的，但它们表明DRD3基因可能在寻求刺激得分高的个体的药物依赖易感性中发挥作用。这一假设与DRD3在介导动物对滥用药物的反应中的作用以及Bal I多态性纯合性与精神分裂症患者药物滥用之间的关联是一致的（见克雷布斯等人的配套文章）。
