IN VIVO DISTRIBUTION OF LITHIUM IN RAT BRAIN

锂（Li）是治疗双相情感障碍的首选，但它有 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研究是研究李集中在哪里 人脑 这是基于这样一种观点，即李克强将集中精力 与其活动相关的大脑部位。 例如，如果Li作用于 胆碱能途径优先于去甲肾上腺素能途径， 预期皮质中的浓度可能高于髓质、中脑或 小脑 动物研究表明，锂的非均匀分布 在哺乳动物的大脑中，但这在动物中很难研究， 通过体外方法或以任何方式在人类中以一致的方式。 对李的作用机制进行“解剖”的另一个方面是 细胞内分数在特定的大脑区域，鉴于 推测的作用位点是细胞内的。 7 Li同位素的磁共振（MR）成像是一种用于 绘制动物和人脑中Li的空间分布图。 在 本建议将测量Li的定量分布， 在大鼠脑中的体内。 将结果与分布进行比较 在分离和切片冷冻大脑后， 随后通过原子吸收分光光度法进行分析， 体外7 Li NMR分析。 磁共振自旋弛豫时间（T1和T2）图像 也将获得，以确保定量结果，并提供 关于离子-组织相互作用的信息和细胞内-组织相互作用的图。 细胞外浓度比 本研究结果将厘清李鸿章在 脑和细胞内与细胞外浓度的问题。 这些研究将作为未来试图将李 测量的体内脑生物化学局部变化的分布 通过局部31 P和1H MR光谱，以及在人类中的类似研究。

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.