THE IRON-DOPAMINE CONNECTION

本项目的具体目标是确定脑铁浓度的变化，作为一种自然的表型变异，或作为增强的表型引起的饮食铁限制，导致DA合成，释放，再摄取和动力学的改变，以及它们对运动反射活动和运动活动的昼夜节律调节的相关影响。本计画的长期计画是建立一个RLS的动物模型，但近期的重点是建立一个探讨铁与多巴胺能系统关系的生物模型。在这个项目中，我们利用两个品系的重组近交系小鼠来探索脑铁变化可以改变DA系统和相关行为的潜在机制。 目前项目的目标是： 目的1：确定在昼夜循环的活动期和非活动期，脑铁变化对DA代谢的影响程度。 目的2：评估脑铁变化导致DA通路调节的行为改变的程度。 目的3：确定在何种程度上，脑铁的变化将改变“正常”DA反应的慢性DA受体激动剂治疗。 目的4：探讨长期使用左旋多巴治疗如何影响目的2中探索的行为。

The specific goal of this project is to determine the extent to which variations in brain iron concentration, that occur as a natural phenotypic variation, or as augmented phenotypes induced by dietary iron restriction, result in alterations of DA synthesis, release, re-uptake, and kinetics, and their associated impact upon motor reflex activity and circadian regulation of motor activity. The long-term plan of this project is to establish an animal model for RLS, but the immediate focus is to establish a biological model for exploring the relationship of iron to the dopaminergic system. In this project, we utilize two strains of recombinant inbred strains of mice to explore the potential mechanisms through which brain iron variances can alter the DA system, and associated behaviors. The aims of the current project are: Aim 1: To determine the extent to which brain iron variances can effect DA metabolism during the active and inactive phases of the diurnal cycle. Aim 2: To assess the degree to which brain iron variance results in alterations in behaviors regulated by DA pathways. Aim 3: To determine the extent to which brain iron variance will alter the "normal" DA response to chronic DA agonist treatment. Aim 4: To explore how chronic treatment with L-dopa will affect the behaviors explored in Aim 2.