SEARCH

SEARCH BY CITATION

Keywords:

  • Antidepressants;
  • [3H]Paroxetine;
  • [3H]Ketanserin

Abstract

This study was undertaken to investigate the effect of chronic treatment with fluoxetine, a selective serotonin uptake inhibitor used widely in the treatment of depression, on the distribution and density of 5-HT uptake sites, 5-HT2 receptors, and vesicular amine uptake sites in rat brain. Fluoxetine (10 mg/kg i. p.) was administered daily for 21 days. The density of 5-HT uptake sites labelled by [3H]paroxetine, 5-HT2 receptors labelled by [3H]ketanserin in presence of tetrabenazine and vesicular amine uptake sites labelled by [3H]ketanserin in the presence of mianserin were measured by quantitative autoradiography in 22 areas of rat brain, using coronal tissue sections. Chronic administration of fluoxetine produced significant increases in the density of 5-HT uptake sites in layers of frontoparietal cortex (by 32–43%), of striate cortex (by 55%), in CA1 field of hippocampus (by 111%) and in superior colliculus (by 20%). Fluoxetine treatment also resulted in upregulation of 5-HT2 receptors in layers of frontparietal cortex (31–38%) and in CA2-3 fields of hippocampus (by 39%). The density of tetrabenazine-sensitive vesicular amine uptake sites in the caudate-putamen was also significantly increased (by 66%). The observed alterations in 5-HT uptake site and 5-HT2 receptor densities are likely a part of adaptive neuronal changes that occur after chronic administration of fluoxetine and may be related to the antidepressant effect of the drug. © 1993 Wiley-Liss, Inc.