EFFECTS OF DOPAMINE AND DOPAMINE RECEPTOR POLYMORPHISMS ON EXPERIENCE-DEPENDENT

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 拟议的研究项目将集中在多巴胺相关基因的三种不同多态性上，这些基因改变了中枢神经系统多巴胺的可用量。 受试者将首先筛选TMS合格性，然后筛选这些多巴胺相关多态性。 将邀请属于所需基因型组的受试者进一步参与研究。 这些受试者将参加两种随机化条件，一种是受试者在运动技能训练前接受左旋多巴，另一种是安慰剂。据推测，神经生理学和行为的措施，改善经验依赖性活动将进一步改善时，在设置中检查增加的中枢神经系统多巴胺水平，这种增强将不同的多巴胺受体基因型。对动物、健康人和患者的研究提供了证据，表明这些基因和多态性与本文研究的皮质可塑性有合理的相关性，因此是评估遗传影响的良好候选者。因变量将是皮质可塑性的经颅磁刺激（TMS）测量和学习的行为测量，其特征在于完成时间和大理石导航任务的错误。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed research project will focus on three different polymorphisms in dopamine-related genes which alter the amount of available CNS dopamine. Subjects will initially be screened for TMS eligibility, and then for these dopamine-related polymorphisms. Subjects falling into the desired genotype groups will be invited to participate further. These subjects will participate in two randomized conditions, one in which the subject receives levodopa prior to motor skill training and one with a placebo. It is hypothesized that neurophysiological and behavioral measures that improve with experience-dependent activity will further improve when examined in the setting of increased CNS dopamine levels; and that this enhancement will vary in relation to dopamine receptor genotype. Studies with animals, healthy humans and patients provide evidence that these genes and polymorphisms are reasonably associated with the cortical plasticity being studied here, and therefore are good candidates for evaluating genetic influences. Dependent variables will be transcranial magnetic stimulation (TMS) measures of cortical plasticity and behavioral measures of learning, as characterized by time to completion and errors on a marble navigation task.