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Antidepressant Drugs Inhibit a Gial 5‐Hydroxytryptamine Transporter in Rat Brain
Author(s) -
Bel Nuria,
Figueras Gloria,
Vilaró M. Teresa,
Suñol Cristina,
Artigas Francesc
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01530.x
Subject(s) - serotonergic , citalopram , serotonin , reuptake , endocrinology , serotonin transporter , fluvoxamine , p chloroamphetamine , medicine , pharmacology , paroxetine , chemistry , antidepressant , biology , fluoxetine , hippocampus , receptor
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.