MODULATION OF BRAIN OPIOIDS AND TACHYKININS BY NEUROTRANSMITTER SYSTEM

该项目的目标是：1）了解基本的 阿片肽（脑啡肽和强啡肽）的生物合成过程 和速激肽（P物质）系统，2）阐明如何 经典的神经递质系统，如多巴胺（DA）相互作用 与阿片肽和速激肽在基底神经节。 以前的研究表明，阻断多巴胺能 传输增加脑啡肽的生物合成，但 降低基底神经节中强啡肽和速激肽的含量。 这项研究检查了增强多巴胺能神经的作用， 阿片肽和速激肽表达的传递 基因. 为此，阿扑吗啡，一种DA受体激动剂，和 使用了D-苯丙胺、DA-苯丙胺类兴奋剂。 重复注射 DA受体激动剂增加了mRNA的丰度， P物质和强啡肽的肽含量，但不包括脑啡肽 在纹状体。为了确定是否重复的影响 注射多巴胺激动剂或拮抗剂的肽是一个 对黑质纹状体DA通路的直接作用或间接作用 通过其他脑区， （6-DHDA）损伤模型。 黑质纹状体DA变性 神经元阻止了D-苯丙胺诱导的水平增加 强啡肽和P物质的含量 与此相反， 阿扑吗啡引起的这两种水平的增加 与对照组相比， 与对侧病变侧，大概是由于 DA受体的超敏感性。 引人关注的是 阿扑吗啡诱导的强啡肽增强 P物质仅在消耗超过90%的大鼠中出现 多巴胺的含量 这一现象可以用我们的 最近的发现，纹状体DA的释放通过测量 微透析过程在大鼠中几乎保持正常， 6-DHDA损伤可使纹状体DA耗竭90%以上。 这些结果 证明了黑质纹状体的可塑性 以维持其传输功能。

The objectives of this project were: 1) to understand the basic biosynthetic process of opioid peptide(enkephalin and dynorphin) and tachykinin (substance P) systems, 2) to elucidate how the classical neurotransmitter systems, such as dopamine (DA) interact with opioid peptides and tachykinins in the basal ganglia. Previous works have shown that blockade of dopaminergic transmission increases the biosynthesis of enkephalins, but decreases that of dynorphins and tachykinins in the basal ganglia. This study examined the effects of enhanced dopaminergic transmission on the expression of opioid peptide and tachykinin genes. For this purpose, apomorphine, a DA receptor agonist, and D-amphetamine, a DA releaser were employed. Repeated injections of either DA agonist increased the abundance of mRNA and the peptide content of substance P and dynorphin, but not enkephalin in the striatum. To determine whether the effects of repeated injections of DA agonists or antagonists on the peptides were a direct action on the nigrostriatal DA pathway or an indirect effect through other brain regions, a unilateral nigral 6-hydroxydopamine (6-DHDA) lesion model was used. Degeneration of nigrostriatal DA neurons prevented the D-amphetamine-induced increase in the levels of dynorphin and substance P in the basal ganglia. In contrast, the apomorphine-induced increase in the levels of these two peptides were greatly enhanced in the lesioned side as compared with the contralateral unlesioned side, presumably due to the supersensitivity of the DA receptors. It is interesting to note that the potentiation of apomorphine-induced increases in dynorphin and substance P only occurred in rats with more than 90% depletion of DA in the striatum. This phenomenon can be interpreted by our recent finding that the release of striatal DA measured by microdialysis procedure remained almost normal in rats with less than 90% depletion of striatal DA by 6-DHDA lesion. These results demonstrate the unusual great plasticity of the nigrostriatal pathway to maintain its transmission function.