Freimer M, Kranzler H, Satel S, Lacobelle J, Skipsey K, Charney D, Gelernter J
Department of Psychiatry, Yale University School of Medicine and West Haven VA Medical Center, West Haven, CT 06516, USA.
Addict Biol. 1996;1(3):281-7. doi: 10.1080/1355621961000124896.
Cocaine is thought to act in the brain primarily by blocking dopamine re-uptake. The dopamine D3 receptor (genetic locus DRD3) is localized to brain regions that have been implicated in the reinforcing effects of a number of substances of abuse, including cocaine. The DRD3 coding region contains a polymorphism identifiable as a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This polymorphism leads to an amino acid substitution at position 9 in the extracellular N-terminus of the D3 dopamine receptor. We examined alleles of the DRD3 gene in cocaine dependence using a genetic association strategy in samples of 62 white and 62 black cocaine-dependent individuals. Comparisons were made with local (Connecticut) control subjects for both groups, and with a larger sample of literature controls (for the white subjects) and a contrast group of schizophrenic patients (for the black subjects). No association was found between cocaine dependence and DRD3 alleles in either group (Bonferroni corrected). There was a significant difference in allele frequency between whites and blacks. These results are consistent with no role for genetic variation of the D3 dopamine receptor in susceptibility to cocaine dependence.
可卡因被认为主要通过阻断多巴胺再摄取在大脑中发挥作用。多巴胺D3受体（基因座DRD3）定位于与包括可卡因在内的多种滥用物质的强化作用有关的脑区。DRD3编码区包含一种可鉴定为聚合酶链反应限制性片段长度多态性（PCR-RFLP）的多态性。这种多态性导致D3多巴胺受体细胞外N端第9位氨基酸发生替换。我们在62名白人和62名黑人可卡因依赖个体的样本中，采用遗传关联策略研究了DRD3基因的等位基因。两组均与当地（康涅狄格州）对照受试者进行比较，白人受试者与更大样本的文献对照进行比较，黑人受试者与精神分裂症患者的对比组进行比较。两组中可卡因依赖与DRD3等位基因之间均未发现关联（经Bonferroni校正）。白人和黑人之间的等位基因频率存在显著差异。这些结果表明，D3多巴胺受体的基因变异在可卡因依赖易感性中不起作用。
