IN VIVO DISTRIBUTION OF LITHIUM IN RAT BRAIN

锂(Li)是治疗双相情感障碍的首选药物，但它确实 一种未知的作用机制。澄清起源的一种方法 李的情绪稳定作用的一个方面是研究李集中在哪里 人脑。这是基于这样一个概念，即李将专注于 与它的行动相关的大脑区域。例如，如果李对 胆碱能途径优先于去甲肾上腺素途径，高LI 皮质的浓度可能比延髓、中脑或 小脑。动物研究表明，锂的分布不均匀 在哺乳动物的大脑中，但这一直很难在动物身上进行研究 通过体外方法或以任何方式在人体内以一致的方式。 “解剖”李氏作用机制的另一个方面是 特定脑区的细胞内分数，考虑到 推测的作用部位是细胞内。 7Li同位素的磁共振(MR)成像是一种用于 绘制LI在动物和人脑中的空间分布图。在……里面 根据这一建议，锂的数量分布将以 在大鼠脑内的活体。结果将与分布进行比较 在分离和切片冰冻脑后发现的同一只大鼠 以及随后的原子吸收光谱分析和In 体外7Li核磁共振分析。磁共振自旋弛豫时间(T1和T2)图像 也将被收购，以确保量化结果，并提供 关于离子-组织相互作用的信息和细胞内-组织相互作用的地图 胞外浓度比。 这项研究的结果将澄清李在 大脑和细胞内浓度与细胞外浓度之间的关系。 这些研究将作为未来尝试将李 脑生化在体内的分布与局部变化的测量 通过本地化的31P和1H磁共振波谱，以及对人类的类似研究。

Lithium (Li) is the treatment of choice for bipolar disorder, but it has an unknown mechanism of action. One approach to clarifying the origin of Li's mood stabilizing effect is to study where Li concentrates in human brain. This is based on the notion that Li would concentrate at brain sites relevant to its action. For example, if Li acts on cholinergic pathways in preference to noradrenergic pathways, higher Li concentration might be expected in cortex than in medulla, midbrain, or cerebellum. Animal studies suggest that nonuniform distribution of Li in mammalian brain, but this has been difficult to study in animals in a consistent manner by in vitro methods, or in humans in any manner. Another aspect of the "anatomy" of Li's mechanism of action is the intracellular fraction in a particular brain region, given that the presumed site of action is intracellular. Magnetic resonance (MR) imaging of the 7Li isotope is a technique for mapping the spatial distribution of Li in animal and human brain. In this proposal the quantitative distribution of Li will be measured in vivo in rat brain. The results will be compared to the distribution found for the same rat after isolation and sectioning of the frozen brain and subsequent analysis by atomic absorption spectrophotometry and in vitro 7Li NMR analysis. The MR spin relaxation time (T1 and T2) images will also be acquired to insure quantitative results, and to provide information on ion-tissue interactions and a map of the intracellular-to- extracellular concentration ratio. The results of this study will clarify the "anatomy" of Li's actions in brain and the issue of intracellular vs. extracellular concentration. These studies will serve as a prelude to future attempts to correlate Li distribution with local changes in brain biochemistry in vivo as measured by localized 31P and 1H MR spectroscopies, and similar studies in humans.