MODULATION OF BRAIN OPIOIDS AND TACHYKININS BY NEUROTRANSMITTER SYSTEM

主要目的是描述多巴胺能神经肽的控制 在基底神经节的稳态，通过操纵多巴胺能紧张。 我们实验室的早期研究表明， 每天注射氟哌啶醇， 一种选择性阻断多巴胺受体的抗精神病药物， 脑啡肽水平的大幅增加，在那些大脑区域丰富 与多巴胺神经支配，如纹状体和脑桥核。 随后，我们进行的研究表明，慢性氟哌啶醇 处理还提高了前体和mRNA编码的水平， 脑啡肽原根据这些结果，我们得出结论， 氟哌啶醇对多巴胺能传递的长期阻断 促进脑啡肽的生物合成。这一结论进一步 我们在用6-羟基多巴胺治疗的大鼠中的发现支持了这一点。变化 脑啡肽及其mRNA在6-羟多巴胺损伤后的变化趋势一致 从氟哌啶醇实验中获得的那些。这两个结果 实验提供了强有力的证据表明，紧张性抑制影响DA 纹状体脑啡肽的生物合成研究扩展到 表征多巴胺能对纹状体强啡肽和P物质的控制 系统.与脑啡肽相反，我们的数据显示多巴胺发挥了 对两种肽的生物合成的紧张性兴奋性影响， 多巴胺能阻断剂降低了这些肽的水平， 各自的mRNA。另一系列实验研究了 多巴胺能传递（阶段控制）对周转的增强作用 阿片肽和P物质。结果表明， 对强啡肽的转换产生阶段性兴奋性影响， P物质，但不是脑啡肽。多巴胺对脑电活动的时相调节 强啡肽和P物质可能与以下情况有关， 动物处于压力下，黑质纹状体多巴胺能传递 增强

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.