Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans
Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans
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DOI：
10.1038/sj.npp.1300025
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发表时间：
2003-02-01
影响因子：
7.6
通讯作者：
Price, LH
中科院分区：
文献类型：
--
作者：
Carpenter, LL;Anderson, GM;Price, LH
许多研究报告称，长期服用选择性血清素再摄取抑制剂（SSRls）后，人腰部脑脊液（CSF）中主要血清素代谢物5-羟基吲哚乙酸（5-HIAA）的浓度降低。这种减少被认为是细胞外血清素升高的结果，并且是通过血清素周转的末端自身受体反馈抑制介导的。我们希望研究 SSRI 给药对人脑脊液 5-HIAA 的先前未经检验的急性影响。在八名健康成年人中，以随机、双盲的方式，在单次口服 40 mg SSRI 帕罗西汀 (PAR) 或匹配安慰剂之前和之后，采用连续腰椎穿刺 (LP) 程序收集脑脊液样本。服用安慰剂后，CSF 5-HIAA 浓度没有变化，但在 PAR 后 3 小时显示出统计学上显着的平均增加 27%。我们的研究结果与报道的人类长期SSRI治疗后CSF 5-HIAA的减少以及对动物急性或长期施用SSR1后脑细胞外5-HIAA的减少形成对比。
A number of studies have reported decreased human lumbar cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), following chronic administration of selective serotonin reuptake inhibitors (SSRls). This decrease has been thought to be a consequence of elevated extracellular serotonin and to be mediated through terminal autoreceptor feedback inhibition of serotonin turnover. We wished to study the previously unexamined acute effects of SSRI administration on human CSF 5-HIAA. A serial lumbar puncture (LP) procedure was used to collect CSF samples before and after a single oral 40 mg dose of the SSRI paroxetine (PAR) or matching placebo in eight healthy adult humans in a randomized, double-blind fashion. CSF 5-HIAA concentrations did not change following placebo, but showed a statistically significant 27% mean increase 3 h following PAR. Our findings stand in contrast to the decreases reported for CSF 5-HIAA after chronic SSRI treatment in humans and the decreases seen in brain extracellular 5-HIAA after acute or chronic administration of SSRls to animals.