EFFECTS OF DOPAMINE AND DOPAMINE RECEPTOR POLYMORPHISMS ON EXPERIENCE-DEPENDENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项拟议的研究项目将专注于多巴胺相关基因的三种不同多态，它们改变了中枢多巴胺的可用数量。受试者将首先接受TMS资格的筛查，然后再筛查这些与多巴胺相关的多态。属于所需基因组的受试者将被邀请进一步参与。这些受试者将参加两个随机的条件，一个是受试者在运动技能训练之前接受左旋多巴治疗，另一个是安慰剂治疗。假设在中枢神经系统多巴胺水平升高的情况下，改善经验依赖活动的神经生理和行为测量将进一步改善；这种增强将因多巴胺受体基因而异。对动物、健康人和患者的研究提供了证据，证明这些基因和多态与这里正在研究的皮质可塑性合理相关，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)测量和学习行为测量，其特征是完成大理石导航任务的时间和错误。

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.