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Título: | Reduction of serotonergic function in rat brain by tryptophan depletion: effects in control and fluvoxamine-treated rats |
Autor: | Bel, Nuria; Artigas, Francesc CSIC ORCID | Palabras clave: | Antidepressants Tryptophan depletion 5-Hydroxytryptamine synthesis 5-Hydroxytryptamine (5-HT) release Intracerebral microdialysis |
Fecha de publicación: | ago-1996 | Editor: | John Wiley & Sons | Citación: | Journal of Neurochemistry 67 (2) : 669-676 (1996) | Resumen: | 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 (∼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. | Versión del editor: | http://dx.doi.org/10.1046/j.1471-4159.1996.67020669.x | URI: | http://hdl.handle.net/10261/34765 | DOI: | 10.1046/j.1471-4159.1996.67020669.x | ISSN: | 0022-3042 | E-ISSN: | 1471-4159 |
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