Persico A M, Bird G, Gabbay F H, Uhl G R
Molecular Neurobiology Branch, National Institute on Drug Abuse/National Institutes of Health, Bethesda, MD, USA.
Biol Psychiatry. 1996 Oct 15;40(8):776-84. doi: 10.1016/0006-3223(95)00483-1.
Several lines of evidence suggest that presence of a D2 dopamine receptor (DRD2) gene variant marked by TaqI restriction fragment length polymorphisms (RFLPs) might contribute to vulnerability to substance abuse. Psychostimulants display the most robust enhancement of dopamine activity in mesolimbic/mesocortical circuits important for behavioral reward. The present study tests the hypothesis that a DRD2 gene variant might be more prominent in polysubstance users who preferentially use psychostimulants than in addicts with preferential opiate use or in those with no drug preference. Polysubstance users with histories of heavy daily preferential psychostimulant use more often displayed one or two copies of the TaqI A1 (27/62 = 43.5% vs 33/119 = 27.7% for controls), and B1 (20/62 = 32.3% vs 23/119 = 19.8% for controls) markers at the DRD2 locus. DRD2 gene marker distributions in abusers with more prominent opiate use, or those with no history of drug preference, were similar to control genotypes. Psychostimulant-preferring drug users also reported earlier onset of psychostimulant use. Our data are consistent with the hypothesis that DRD2 gene variants marked by these polymorphisms may work, probably in concert with other genetic and environmental factors, to enhance vulnerability to psychostimulant abuse.
多项证据表明，由TaqI限制性片段长度多态性（RFLP）标记的D2多巴胺受体（DRD2）基因变异可能会增加药物滥用的易感性。精神兴奋剂在对行为奖赏至关重要的中脑边缘/中脑皮质回路中，能最有力地增强多巴胺活性。本研究检验了这样一个假设：与优先使用阿片类药物的成瘾者或无药物偏好者相比，优先使用精神兴奋剂的多药滥用者中，DRD2基因变异可能更为突出。有每日大量优先使用精神兴奋剂史的多药滥用者，在DRD2基因座上更常出现TaqI A1（27/62 = 43.5%，而对照组为33/119 = 27.7%）和B1（20/62 = 32.3%，而对照组为23/119 = 19.8%）标记的一个或两个拷贝。在优先使用阿片类药物更突出的滥用者或无药物使用史者中，DRD2基因标记分布与对照基因型相似。优先使用精神兴奋剂的吸毒者也报告说开始使用精神兴奋剂的时间更早。我们的数据与这样的假设一致，即由这些多态性标记的DRD2基因变异可能起作用，可能与其他遗传和环境因素协同作用，增加对精神兴奋剂滥用的易感性。
