Karoum F, Chrapusta S J, Egan M F
Neuropsychiatry Branch, National Institute of Mental Health, Washington, D.C.
J Neurochem. 1994 Sep;63(3):972-9. doi: 10.1046/j.1471-4159.1994.63030972.x.
3-Methoxytyramine (3-MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used, respectively, to assess the dynamics of dopamine (DA) release and turnover in the rat frontal cortex, nucleus accumbens, and striatum. Assuming total (re)uptake and metabolism of released DA are relatively uniform among the three brain regions, a simplified two pool model was used to assess the metabolic fate of released DA. Under basal conditions, 3-MT formation was found to comprise > 60% of total DA turnover (sum of 3-MT plus DOPAC rates of formation) in the frontal cortex, and not more than 15% in the nucleus accumbens and striatum. Haloperidol increased the 3-MT rate of formation to a greater extent in the frontal cortex than in the two other regions. Clozapine increased the 3-MT rate of formation in the frontal cortex and decreased it in the striatum. Both drugs increased DOPAC rate of formation in the frontal cortex and nucleus accumbens. It was elevated by haloperidol but not clozapine in the striatum. It is concluded that (1) O-methylation is a prominent step in the catabolism of DA in the frontal cortex under both physiological conditions and after acute treatment with antipsychotics, (2) 3-MT is the major metabolite of released DA in the frontal cortex and possibly also in the nucleus accumbens and striatum, (3) in contrast to the frontal cortex, most of the DOPAC in the nucleus accumbens and striatum appear to originate from intraneuronal deamination of DA that has not been released, (4) because presynaptic uptake and metabolism of DA give rise to DOPAC, whereas postsynaptic uptake and metabolism produced both DOPAC and 3-MT, the ratio of 3-MT to DOPAC rates of formation can be a useful index of reuptake inhibition.
采用3-甲氧基酪胺（3-MT）和3,4-二羟基苯乙酸（DOPAC）的生成速率，分别评估大鼠额叶皮质、伏隔核和纹状体中多巴胺（DA）释放和周转的动态变化。假设释放的DA在这三个脑区的总（再）摄取和代谢相对一致，使用简化的双池模型来评估释放的DA的代谢命运。在基础条件下，发现额叶皮质中3-MT的生成占总DA周转（3-MT与DOPAC生成速率之和）的60%以上，而在伏隔核和纹状体中不超过15%。氟哌啶醇使额叶皮质中3-MT的生成速率增加的程度大于其他两个区域。氯氮平增加了额叶皮质中3-MT的生成速率，而降低了纹状体中3-MT的生成速率。两种药物均增加了额叶皮质和伏隔核中DOPAC的生成速率。在纹状体中，DOPAC的生成速率被氟哌啶醇提高，但未被氯氮平提高。得出以下结论：（1）在生理条件下和抗精神病药物急性治疗后，O-甲基化是额叶皮质中DA分解代谢的一个重要步骤；（2）3-MT是额叶皮质中释放的DA的主要代谢产物，在伏隔核和纹状体中可能也是如此；（3）与额叶皮质不同，伏隔核和纹状体中的大多数DOPAC似乎源自未释放的DA的神经元内脱氨基作用；（4）由于DA的突触前摄取和代谢产生DOPAC，而突触后摄取和代谢产生DOPAC和3-MT，3-MT与DOPAC生成速率的比值可作为再摄取抑制的有用指标。
