MODULATION OF BRAIN OPIOIDS AND TACHYKININS BY NEUROTRANSMITTER SYSTEM

主要目标是表征多巴胺能对神经肽的控制。 基底节的动态平衡，通过操控多巴胺能张力。 我们实验室的早期研究表明，长期封锁 每日注射氟哌啶醇对多巴胺能传递的影响 选择性阻断多巴胺受体的抗精神病药物导致 丰富的脑区脑啡肽水平显著升高 有多巴胺神经支配，如纹状体和伏隔核。 随后，我们进行了研究，表明慢性氟哌啶醇 治疗还提高了前体和编码mrna的水平。 纹状体中的前脑啡肽。根据这些结果，我们得出结论 氟哌啶醇长期阻断多巴胺能传递 促进脑啡肽的生物合成。这一结论是进一步的 我们在用6-羟基多巴胺治疗的大鼠身上的发现支持了这一点。变化 6-羟基多巴胺损毁后脑啡肽及其mRNA的表达 与从氟哌啶醇实验中获得的药物相比较。这两项研究的结果 实验为多巴胺的紧张性抑制作用提供了强有力的证据 纹状体脑啡肽的生物合成。研究范围扩展到 多巴胺能对纹状体强啡肽和P物质的控制特征 系统。与脑啡肽不同的是，我们的数据显示，多巴胺 紧张性兴奋对两种多肽生物合成的影响，如 多巴胺能阻断可降低这些多肽及其受体的水平。 各自的mRNA.另一系列实验考察了 促进多巴胺能传递(时相控制)对周转的影响 阿片肽和P物质。结果表明，多巴胺 时相兴奋对强啡肽周转的影响 P物质，但不是脑啡肽。多巴胺对血管内皮细胞的时相调节 强啡肽和P物质可能与以下情况有关 动物处于应激状态，黑质纹状体多巴胺能传递 增强版。

The major goal was to characterize dopaminergic control over neuropeptide homeostasis in the basal ganglia, by manipulating dopaminergic tone. Early studies from our laboratory demonstrated that long-term blockade of dopaminergic transmission by daily injections of haloperidol, an antipsychotic drug which selectively blocks dopamine receptors, caused a large increase in the level of enkephalin in those brain areas enriched with dopamine innervation, such as the striatum and nucleus accumbens. Subsequently, we undertook studies which showed that chronic haloperidol treatment also elevated the levels of precursor and mRNA encoding proenkephalin in the striatum. Based on these results, we concluded that long-term blockade of dopaminergic transmission by haloperidol accelerated the biosynthesis of enkephalin. This conclusion was further supported by our findings in rats treated with 6-hydroxydopamine. Changes of enkephalin and its mRNA after 6-hydroxydopamine lesion were identical to those obtained from the haloperidol experiment. Results from these two experiments present strong evidence for a tonic inhibitory influence o DA on the biosynthesis of striatal enkephalin. Studies were extended to characterize dopaminergic control over striatal dynorphin and substance P systems. In contrast to enkephalin, our data showed that dopamine exerted a tonic excitatory influence on the biosynthesis of both peptides, as dopaminergic blockade reduced the levels of these peptides and their respective mRNA. Another series of experiments examined the influence of enhancement of dopaminergic transmission (phasic control) on the turnover of opioid peptides and substance P. Results indicated that dopamine exerted phasic excitatory influence on the turnover of dynorphin and substance P, but not on enkephalin. The phasic regulation of dopamine on dynorphin and substance P may have some relevance to conditions where animals are under stress and nigrostriatal dopaminergic transmission is enhanced.