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首页> 外文期刊>Biological psychiatry >Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior.
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Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior.

机译：多巴胺受体D4多态性预测L-DOPA对赌博行为的影响。

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BACKGROUND: There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. METHODS: We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. RESULTS: Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. CONCLUSIONS: These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.
机译：背景：有充分的证据表明，接受多巴胺能药物治疗的帕金森氏病患者亚组会产生某些行为上瘾，例如病理性赌博。这些患者中只有一个亚组发生病理性赌博，这一事实表明多巴胺能药物治疗与个体易感性因素之间存在相互作用。这些都是潜在的遗传来源，因为对健康受试者的研究表明，病理性赌博的脆弱性可能与多巴胺受体D4（DRD4）基因的变异有关。使用药物遗传学方法，我们研究了该基因的变异如何调节多巴胺能刺激对健康受试者赌博行为的影响。方法：我们向200名因DRD4基因多态性而均已进行基因分型的健康男性受试者服用了300 mg L-二羟基苯丙氨酸（L-DOPA）或安慰剂。在L-DOPA管理60分钟后，受试者进行了赌博任务。结果：不考虑遗传信息，与安慰剂相比，L-DOPA给药并未导致赌博倾向的增加。但是，正如预期的那样，在施用L-DOPA后，个体的DRD4多态性导致了赌博行为的变化。携带至少一个7重复等位基因拷贝的受试者在多巴胺能刺激后表现出更高的赌博倾向。结论：这些发现表明，DRD4基因的遗传变异决定了个体对多巴胺能药物攻击的赌博行为。通过提供基因型方法来确定个体对病理性赌博的敏感性，它们可能对帕金森氏病患者的治疗产生影响，也可能提供对成瘾行为基础的脆弱性机制的见解。

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