Bel N, Artigas F
Department of Neurochemistry, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, Spain.
J Neurochem. 1996 Aug;67(2):669-76. doi: 10.1046/j.1471-4159.1996.67020669.x.
The administration of tryptophan (Trp)-free amino acid mixtures to depressed patients responding to serotonin [5-hydroxytryptamine (5-HT)] uptake inhibitors (SSRIs) worsens their clinical state. This procedure reduces Trp availability to brain and thus impairs 5-HT synthesis. We have examined the influence of Trp depletion on extracellular 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the rat brain using in vivo microdialysis. The treatment with the SSRI fluvoxamine significantly increased 5-HT content in dialysates from frontal cortex, as compared with control rats (10.2 +/- 2.7 vs. 3.1 +/- 0.4 fmol per fraction), whereas 5-HIAA was unaffected. Food deprivation for 20 h reduced dialysate 5-HT content to almost control values in fluvoxamine-treated rats (10.2 +/- 2.7 vs. 4.3 +/- 0.6 fmol per fraction) but did not alter dialysate 5-HIAA content (7.8 +/- 0.4 vs. 7.2 +/- 0.5 pmol per fraction). The administration of Trp-free amino acid mixtures to fluvoxamine-treated rats significantly attenuated the release of 5-HT in frontal cortex (approximately 50%) and, to a lesser extent, in the midbrain raphe nuclei. This effect was more marked in rats not deprived from food before the experiments (67% reduction of dialysate 5-HT content in frontal cortex) and was absent in control rats (treated with saline). In contrast, dialysate 5-HIAA was markedly affected by Trp depletion in all groups, including controls (65-75% reductions). These data show that the administration of an amino acid mixture with the same composition and dose (in milligrams per kilogram of body weight) as those inducing a severe mood impairment in depressed patients reduces 5-HT and 5-HIAA concentrations in brain dialysates. The reduction of 5-HT release, however, occurs only in animals previously treated with the antidepressant fluvoxamine for 2 weeks, which would be consistent with a marked reduction of 5-HT-mediated transmission in treated depressed patients but not in healthy controls.
给对血清素[5-羟色胺（5-HT）]摄取抑制剂（SSRI）有反应的抑郁症患者服用不含色氨酸（Trp）的氨基酸混合物会使他们的临床状态恶化。这一过程会减少大脑中色氨酸的可利用性，从而损害5-羟色胺的合成。我们使用体内微透析技术研究了色氨酸耗竭对大鼠大脑细胞外5-羟色胺和5-羟吲哚乙酸（5-HIAA）浓度的影响。与对照大鼠相比，用SSRI氟伏沙明治疗显著增加了额叶皮质透析液中的5-羟色胺含量（每部分10.2±2.7皮摩尔对3.1±0.4皮摩尔），而5-HIAA不受影响。在氟伏沙明治疗的大鼠中，禁食20小时使透析液5-羟色胺含量降至几乎对照值（每部分10.2±2.7皮摩尔对4.3±0.6皮摩尔），但未改变透析液5-HIAA含量（每部分7.8±0.4皮摩尔对7.2±0.5皮摩尔）。给氟伏沙明治疗的大鼠服用不含色氨酸的氨基酸混合物显著减弱了额叶皮质中5-羟色胺（约50%）以及中脑缝际核中程度较轻的5-羟色胺释放。这种效应在实验前未禁食的大鼠中更为明显（额叶皮质透析液5-羟色胺含量降低67%），而在对照大鼠（用盐水治疗）中不存在。相比之下，所有组（包括对照组）的透析液5-HIAA都受到色氨酸耗竭的显著影响（降低65 - 75%）。这些数据表明，给抑郁症患者服用与导致严重情绪损害的氨基酸混合物具有相同组成和剂量（每千克体重毫克数）的氨基酸混合物会降低大脑透析液中5-羟色胺和5-HIAA的浓度。然而，5-羟色胺释放的减少仅发生在先前用抗抑郁药氟伏沙明治疗2周的动物中，这与治疗的抑郁症患者中5-羟色胺介导的传递显著减少但健康对照中未减少相一致。
