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Título: | Role of uptake inhibition and autoreceptor activation in the control of 5-HT release in the frontal cortex and dorsal hippocampus of the rat |
Autor: | Hervás, Ildefonso; Queiroz, Claudio M.T.; Adell, Albert CSIC ORCID ; Artigas, Francesc CSIC ORCID | Palabras clave: | 5-hydroxytryptamine 5-HT (5-hydroxytryptamine, serotonin) uptake 5-HT1A receptors 5-HT1B receptors Antidepressants Citalopram fluoxetine frontal cortex hippocampus microdialysis |
Fecha de publicación: | may-2000 | Editor: | John Wiley & Sons | Citación: | British Journal of Pharmacology 130 (1) : 160–166 (2000) | Resumen: | Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT1A and/or terminal 5-HT1B autoreceptor activation in the control of 5-HT output. Fluoxetine (10 mg kg−1 i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT1A receptor antagonist WAY 100635, (0.3 mg kg−1 s.c.) potentiated the effect of fluoxetine only in frontal cortex (to ∼500 % of baseline). Methiothepin (10 mg kg−1 s.c.) further enhanced the 5-HT rise induced by fluoxetine+WAY 100635, to 835±179% in frontal cortex and 456±24% in dorsal hippocampus. Locally applied, methiothepin potentiated the fluoxetine-induced 5-HT rise more in the former area. The selective 5-HT1B receptor antagonist SB-224289 (4 mg kg−1 i.p.) enhanced the effect of fluoxetine (10 mg kg−1 i.p.) in both areas. As with methiothepin, SB-224289 (4 mg kg−1 i.p.) further enhanced the 5-HT increase produced by fluoxetine+WAY 100635 more in frontal cortex (613±134%) than in dorsal hippocampus (353±59%). Locally applied, fluoxetine (10–300 μm; EC50=28–29 μm) and citalopram (1–30 μm; EC50=1.0–1.4 μm) increased the 5-HT output two to three times more in frontal cortex than in dorsal hippocampus. These data suggest that the comparable 5-HT increase produced by systemic fluoxetine in frontal cortex and dorsal hippocampus results from a greater effect of reuptake blockade in frontal cortex that is offset by a greater autoreceptor-mediated inhibition of 5-HT release. As a result, 5-HT autoreceptor antagonists preferentially potentiate the effect of fluoxetine in frontal cortex. | Versión del editor: | http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0703297/pdf http://dx.doi.org/10.1038/sj.bjp.0703297 |
URI: | http://hdl.handle.net/10261/33140 | DOI: | 10.1038/sj.bjp.0703297 | ISSN: | 0007-1188 | E-ISSN: | 1476-5381 |
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