Dopaminergic modulation of serotonin metabolism in rat striatum: a study with dopamine uptake inhibitor GBR-12909.
Dopaminergic modulation of serotonin metabolism in rat striatum: a study with dopamine uptake inhibitor GBR-12909.
复制标题
大鼠纹状体血清素代谢的多巴胺能调节：多巴胺摄取抑制剂 GBR-12909 的研究。
DOI：
10.1016/0024-3205(95)00233-v
复制
发表时间：
1995
期刊：
影响因子：
6.1
通讯作者：
Sivam,SP
中科院分区：
文献类型：
--
作者：
Sivam,SP
以多巴胺（DA）摄取抑制剂GBR 12909（GBR）和新生去多巴胺能神经大鼠模型为工具，研究DA对纹状体5-羟色胺（5-HT）系统的影响。纹状体水平的胺和它们的酸代谢产物（二羟基苯乙酸，DOPAC; 5-羟基吲哚乙酸，5 HIAA）的HPLC测定。单次给药（20 mg/kg）GBR未能影响胺或代谢物的稳态水平。GBR（20 mg/kg/天）重复给药2或4天可降低DA和DOPAC;仅4天给药方案可降低5 HT并升高5 HIAA水平。用6-羟基多巴胺（6 OHDA）进行的新生儿多巴胺能损伤耗尽（> 95%）DA和DOPAC，并增加纹状体中的5 HT和5 HIAA水平。对病变动物给予GBR（20 mg/kg/天，持续4天）未能影响病变诱导的5 HT和5 HIAA水平升高。结果表明，GBR降低了稳态水平的DA，导致在营业额的5 HT是依赖于完整的多巴胺能末梢的存在下的补偿性增加。因此，GBR对5 HT周转的影响是间接的。这些研究为多巴胺能对纹状体5 HT代谢的显著影响提供了进一步支持。
The dopamine (DA) uptake inhibitor, GBR 12909 (GBR) and a neonatal dopaminergic denervated rat model were used as tools to study the influence of DA on the serotonin (5HT) system in the striatum. The striatal levels of the amines and their acid metabolites (dihydroxyphenylacetic acid, DOPAC; 5-hydroxyindoleacetic acid, 5HIAA) were determined by HPLC. The administration of a single dose (20 mg/kg) of GBR failed to affect the steady-state levels of the amines or metabolites. Repeated administration of GBR (20 mg/kg/day) for 2 or 4 days decreased DA and DOPAC; only the 4-day regimen decreased 5HT and increased 5HIAA levels. The neonatal dopaminergic lesion with 6-hydroxydopamine (6OHDA) depleted (> 95%) DA and DOPAC and increased 5HT and 5HIAA levels in the striatum. Administration of GBR (20 mg/kg/day for 4 days) to lesioned animals failed to influence the lesion-induced increases in 5HT and 5HIAA levels. The results suggest GBR decreases the steady-state levels of DA, resulting in a compensatory increase in the turnover of 5HT that is dependent on the presence of intact dopaminergic terminals. Thus, the effect of GBR on 5HT turnover is indirect. The studies provide further support for a prominent dopaminergic influence on striatal 5HT metabolism.