Erblich J, Lerman C, Self D W, Diaz G A, Bovbjerg D H
Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA.
Pharmacogenomics J. 2004;4(2):102-9. doi: 10.1038/sj.tpj.6500227.
Animal models have long implicated dopamine in stress-induced craving for a variety of addictive substances. However, translational studies of dopamine, stress and craving in humans are lacking. Based on the animal literature, this study's objective was to test the hypothesis that cigarette smokers carrying specific variants in dopamine-related genes would have heightened levels of cigarette craving following exposure to a laboratory stressor. Cigarette craving induced by controlled exposure to a laboratory stressor was assessed in healthy adult smokers (n=108) recruited by advertisement. Significantly stronger stress-induced cigarette craving was found for individuals carrying either the DRD2 (D2 dopamine receptor gene) A1, or the SLC6A3 (dopamine transporter gene) nine-repeat allelic variants. Stress-induced craving was markedly higher for those carrying both alleles, compared to those with neither, consistent with the separate biological pathways involved (receptor, transporter). Findings provide strong support for the possibility that dopamine involvement in stress-induced craving well established in animal models also applies to humans, and suggest a potential genetic risk factor for persistent smoking behavior.
长期以来，动物模型表明多巴胺与应激诱导的对多种成瘾物质的渴望有关。然而，关于多巴胺、应激和渴望在人类中的转化研究却很缺乏。基于动物文献，本研究的目的是检验以下假设：携带多巴胺相关基因特定变体的吸烟者在接触实验室应激源后，对香烟的渴望程度会更高。通过广告招募了108名健康成年吸烟者，评估了在受控条件下接触实验室应激源所诱发的对香烟的渴望。结果发现，携带DRD2（D2多巴胺受体基因）A1或SLC6A3（多巴胺转运体基因）九重复等位基因变体的个体，应激诱导的对香烟的渴望明显更强。与两个等位基因都不携带的人相比，同时携带这两个等位基因的人应激诱导的渴望明显更高，这与所涉及的不同生物学途径（受体、转运体）一致。这些发现为动物模型中已充分证实的多巴胺参与应激诱导的渴望也适用于人类这一可能性提供了有力支持，并提示了持续吸烟行为的一个潜在遗传风险因素。
