An In Vivo Study of Dopamine Release and Metabolism in Rat Brain Regions Using Intracerebral Dialysis
An In Vivo Study of Dopamine Release and Metabolism in Rat Brain Regions Using Intracerebral Dialysis
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DOI：
10.1111/j.1471-4159.1986.tb02838.x
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发表时间：
1986-07
影响因子：
4.7
通讯作者：
T. Sharp;T. Zetterström;Urban Ungerstedt
中科院分区：
文献类型：
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作者：
T. Sharp;T. Zetterström;Urban Ungerstedt
使用脑内透析和专门设计的HPLC电化学检测试验，监测卤代乙烷麻醉大鼠脑区域中内源性3，4-二羟基苯乙胺（多巴胺，DA）及其主要代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）的细胞外水平。从纹状体和脑皮层收集的对照灌注液中检测到显著量的DA、DOPAC和HVA。而内侧前额叶皮层表现出较低的单胺水平。灌流液中DA与整个组织中DA的比值表明，在f.与n相比，纹状体和纹状体中，细胞外间隙中的DA含量相对于神经元内的DA含量更高。对照灌注液中的DOPAC/HVA比率根据整个组织测量在区域之间变化。这一比例在n中最高。最低的是f。皮层单胺氧化酶抑制剂帕吉林（100 mg/kg i. p.）导致DOPAC指数下降，但不是HVA，在区域灌注液中，与DA的增加相关的效果。数据表明，细胞外DOPAC在n.纹状体中DOPAC含量最高，纹状体中DOPAC含量最低。皮层细胞外DA代谢物水平的下降速度慢于整个组织的测量。在灌注液中，灌注液中DA的基础量与任何区域的DOPAC和HVA水平或DOPAC营业额之间没有统计学相关性，表明在基础条件下测量大脑中的DA代谢并不能提供良好的DA释放指数。总之，这项研究表明，明确的区域差异，基础DA释放和代谢物水平，代谢物模式，和DOPAC周转率在大鼠大脑中的体内。
Intracerebral dialysis was used with a specifically designed HPLC with electrochemical detection assay to monitor extracellular levels of endogenous 3,4‐dihydroxyphenylethylamine (dopamine, DA) and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in brain regions of the halo‐thane‐anesthetized rat. Significant amounts of DA, DOPAC, and HVA were detected in control perfusates collected from striatum and n. accumbens whereas the medial prefrontal cortex showed lower monoamine levels. The ratio of DA in perfusate to DA in whole tissue suggests that in f. cortex, compared to n. accumbens and striatum, there is a greater amount of DA in the extracellular space relative to the intraneuronal DA content. The DOPAC/HVA ratio in control perfusates varied between regions in accordance with whole tissue measurements. This ratio was highest in n. accumbens and lowest in f. cortex. The monoamine oxidase inhibitor pargyline (100 mg/kg i.p.) caused an exponential decline in DOPAC, but not of HVA, in regional perfusates, an effect that was associated with an increase in DA. The data indicated a higher turnover of extracellular DOPAC in n. accumbens than in striatum and the lowest DOPAC turnover in f. cortex. The rate of decline in extracellular DA metabolite levels was slow compared to whole tissue measurements. In the perfusates there was no statistical correlation between basal amounts of DA in the perfusates and DOPAC and HVA levels or DOPAC turnover for any of the areas, indicating that measurement of DA metabolism in the brain under basal conditions does not provide a good index of DA release. In summary, this study shows clear regional differences in basal DA release and metabolite levels, metabolite patterns, and DOPAC turnover rates in rat brain in vivo.