Sternberg D E, Heninger G R, Roth R H
Life Sci. 1983 May 23;32(21):2447-52. doi: 10.1016/0024-3205(83)90370-3.
Plasma levels of the dopamine (DA) metabolite homovanillic acid (HVA) may be a useful measure of brain HVA production by central DA systems. Even though there is a significant peripheral contribution to plasma HVA, experimental manipulations that alter brain HVA produce parallel changes in plasma HVA levels. This study was designed to assess whether the ability of plasma HVA to reflect haloperidol induced increases in brain HVA could be strengthened by reducing the contribution to plasma HVA from peripheral sources. Debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the brain, was given in a low dose schedule to rats and lowered the peripheral contribution to plasma HVA by between 42 and 68%, resulting in a situation where between 62 and 87% of plasma HVA derived from brain. Using this dose schedule, rats pretreated with debrisoquin displayed a significant increase in plasma HVA following a lower dose of haloperidol than that required in the vehicle pretreated rats. In the debrisoquin pretreated group, a 71% increase in brain HVA was accompanied by a significant 60% increase in plasma HVA, whereas the vehicle pretreated group required a 136% increase in brain HVA to display a significant 50% increase in plasma. These findings indicate that debrisoquin pretreatment improves the reliability of plasma HVA to reflect changes in brain DA metabolism. Plasma HVA samples obtained from humans following debrisoquin may provide a clinically applicable method for assessing brain DA systems in neurologic and psychiatric illness.
多巴胺（DA）代谢产物高香草酸（HVA）的血浆水平可能是衡量中枢DA系统脑内HVA生成量的一项有用指标。尽管外周对血浆HVA有显著贡献，但改变脑内HVA的实验操作会使血浆HVA水平产生平行变化。本研究旨在评估通过减少外周来源对血浆HVA的贡献，是否能够增强血浆HVA反映氟哌啶醇诱导的脑内HVA增加的能力。硫酸异喹胍是一种不进入脑内的单胺氧化酶抑制剂，以低剂量方案给予大鼠，可使外周对血浆HVA的贡献降低42%至68%，从而使血浆HVA的62%至87%来源于脑内。采用该剂量方案，用硫酸异喹胍预处理的大鼠在给予比溶媒预处理大鼠所需剂量更低的氟哌啶醇后，血浆HVA显著增加。在硫酸异喹胍预处理组中，脑内HVA增加71%的同时，血浆HVA显著增加60%，而溶媒预处理组则需要脑内HVA增加136%才能使血浆HVA显著增加50%。这些发现表明，硫酸异喹胍预处理提高了血浆HVA反映脑内DA代谢变化的可靠性。硫酸异喹胍处理后的人类血浆HVA样本可能为评估神经和精神疾病中的脑DA系统提供一种临床适用的方法。
