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Closed Access item Antidepressant drugs inhibit a glial 5-hydroxytryptamine transporter in rat brain

Authors:Bel, Nuria
Figueras, Gloria
Vilaró, Maria Teresa
Suñol, Cristina
Artigas, Francesc
Keywords:Astrocyte cultures microdialysis, Mouse, Rat, Selective serotonin reuptake inhibitors, Tricyclic antidepressants
Issue Date:Aug-1997
Citation:European Journal of Neuroscience 9 (8) : 1728-1738 (1997)
Abstract:We assessed the role of glial cells in the uptake of serotonin (5-hydroxytryptamine, 5-HT). Primary cultures of rat and mouse cortical astrocytes took up and deaminated 5-HT. The antidepressants citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine and sertraline inhibited this process. The presence of the mRNAs for the 5-HT transporter and monoamine oxidase-A (MOA-A) was established in cultured astrocytes and in adult rat brain areas with (midbrain and brainstem) and without (frontal cortex) serotonergic cell bodies after reverse transcription-polymerase chain reaction and hybridization with probes complementary to the cloned neuronal 5-HT transporter and MAO-A. To examine in vivo the role of astrocytes in the elimination of 5-HT from the extracellular brain space, 5-HT was perfused through dialysis probes implanted in the frontal cortex of conscious rats and its concentration was measured at the probe outlet. Tissue 5-HT recovery was dose-dependently inhibited by the concurrent perfusion of citalopram, fluoxetine and paroxetine, showing that it essentially measured uptake through the high-affinity 5-HT transporter. Rats lesioned with 5,7-dihydroxytryptamine (5,7-DHT; 88% reduction of tissue 5-HT) displayed tissue 5-HT recovery slightly higher than sham-operated rats (55 ± 2 vs. 46 ± 3%, P < 0.001), a finding perhaps attributable to the astrogliosis induced by 5,7-DHT denervation. Rats lesioned with 6-hydroxydopamine showed tissue 5-HT uptake similar to controls, suggesting negligible reuptake of 5-HT by catecholaminergic terminals. These results are consistent with the presence of a glial component of 5-HT uptake in the rodent brain, sensitive to antidepressants, which takes place through a 5-HT transporter very similar or identical to that present in neurons.
Publisher version (URL):http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.1997.tb01530.x/abstract
E-ISSNmetadata.dc.identifier.doi = DOI:1460-9568
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