title: Effects of the antidepressant fluoxetine on the subcellular localization of 5-HT1A receptors and SERT.
abstract: Serotonin (5-HT) 5-HT(1A) autoreceptors (5-HT(1A)autoR) and the plasmalemmal 5-HT transporter (SERT) are key elements in the regulation of central 5-HT function and its responsiveness to antidepressant drugs. Previous immuno-electron microscopic studies in rats have demonstrated an internalization of 5-HT(1A)autoR upon acute administration of the selective agonist 8-OH-DPAT or the selective serotonin reuptake inhibitor antidepressant fluoxetine. Interestingly, it was subsequently shown in cats as well as in humans that this internalization is detectable by positron emission tomography (PET) imaging with the 5-HT(1A) radioligand [(18)F]MPPF. Further immunocytochemical studies also revealed that, after chronic fluoxetine treatment, the 5-HT(1A)autoR, although present in normal density on the plasma membrane of 5-HT cell bodies and dendrites, do not internalize when challenged with 8-OH-DPAT. Resensitization requires several weeks after discontinuation of the chronic fluoxetine treatment. In contrast, the SERT internalizes in both the cell bodies and axon terminals of 5-HT neurons after chronic but not acute fluoxetine treatment. Moreover, the total amount of SERT immunoreactivity is then reduced, suggesting that SERT is not only internalized, but also degraded in the course of the treatment. Ongoing and future investigations prompted by these finding are briefly outlined by way of conclusion.
authors: Departments of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, , Montreal, Quebec, Canada H3C 3J7. laurent.descarries@umontreal.ca
authors: Laurent
authors: L
authors: Descarries
authors: Mustaph
authors: M
authors: Riad
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D017660:Autoreceptors / Q000378:metabolism; D002415:Cats; D002462:Cell Membrane / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000928:Antidepressive Agents; D017660:Autoreceptors; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors