TYROSINE DEPLETION, MOOD AND COGNITION IN HEALTHY HUMAN SUBJECTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大脑化学物质允许所有形式的行为发生，包括解决问题、情感和未来定向行动。神经科学家感兴趣的一种化学物质是多巴胺，它存在于整个大脑中，但被认为在促进奖励导向行为和促进工作记忆方面发挥着特殊作用。工作记忆是指当你在为未来的行动而努力时，你把信息记在心里。重要的是，多巴胺似乎促进了这一过程。在多巴胺活性受损的临床条件下，目标导向行为是缺乏的。例子包括精神分裂症、帕金森氏病和苯丙酮尿症。了解这些临床状况的一部分是了解多巴胺系统如何在健康人中发挥作用。这是困难的，因为我们想研究这个系统，而不实际进入大脑或引入特别密集的操作。一种在医院实验室之外研究多巴胺活性的新方法被称为“酪氨酸耗竭”。急性酪氨酸耗竭涉及一次性摄入缺乏参与多巴胺合成的蛋白质的蛋白质混合物。这些蛋白质是酪氨酸和苯丙氨酸。在这项研究中，我们将使用酪氨酸耗竭来降低健康人的多巴胺活性，测量他们的行为反应。我们假设，大脑多巴胺系统活动的短暂降低会微妙地（显着地）损害工作记忆和对奖励刺激的反应。将在受试者间设计中对健康成人进行测试。每个人将在GCRC进行一次门诊访视。访问将持续约7小时。在此期间，将摄入蛋白质饮料，其（a）在大氨基酸蛋白质中平衡（B）缺乏酪氨酸+苯丙氨酸。饮酒后5小时，将通过一系列旨在测量工作记忆的任务来测试认知处理。PI将以粉末形式购买氨基酸，并在研究期间储存在GCRC中。PI还将提供进行认知测试所需的所有设备。需要GCRC资源来制备氨基酸混合物，并在饮用后监测参与者的生命体征。

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. Brain chemicals allow all forms of behavior to take place, including problem solving, emotion, and future directed actions. One chemical that is of interest to neuroscientists is dopamine, which is present throughout the brain but which is thought to play a special role in facilitating reward-directed behavior and in facilitating working memory. Working memory is when you hold information in mind while working toward some future action. Importantly, dopamine appears to facilitate this process. In clinical conditions where dopamine activity is impaired, goal-directed behavior is deficient. Examples include schizophrenia, Parkinson's disease, and phenylketonuria. Part of understanding these clinical conditions is to understand how the dopamine system functions in healthy people. This is difficult, because we would like to study the system without actually going into the brain or introducing a manipulation that is particulary intensive. One new method for studying dopamine activity outside of hospital laboratories is referred to as "tyrosine depletion". Acute tyrosine depletion involves the one-time ingestion of a protein mixture that is deficient in the proteins that are involved in dopamine synthesis. Those proteins are tyrosine and phenylalanine. In this study, we will use tyrosine depletion to lower dopamine activity in healthy people, measuring aspects of their behavior in response. We hypothesize that the transient lowering of activity within the brain's dopamine system will subtly (significantly) impair working memory and responsivity to rewarding stimuli. Healthy adults will be tested in a between-subjects design. Each will make one outpatient visit to the GCRC. The visit will last for approximately seven hours. During this time, a protein drink will be ingested that is either (a) balanced in large amino acid proteins (b) deficient in tyrosine + phenylalanine. Five hours after drink ingestion, cognitive processing will be tested through a battery of tasks designed to measure working memory. The amino acids will be purchsaed in powdered form by the PI and stored for the duration of the study in the GCRC. The PI will also provide all equipment necessary to conduct cognitive testing. GCRC resources are requested to prepare the amino acid mixtures and to monitor partipants' vital signs after drink ingestion.