title: Serotonin 5-HT2C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.
abstract: Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT2C receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT2C receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT2C receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20 mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20 mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT2C receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT2C receptors. Thus, functional 5-HT2C receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.
authors.affiliation: Department of Neurosurgery, Helsinki University Central Hospital, 00029 HUS, Finland. esa-pekka.palvimaki@hus.fi
authors.forename: Esa-Pekka
authors.initials: EP
authors.lastname: Pälvimäki
authors.forename: Hannu
authors.initials: H
authors.lastname: Majasuo
authors.forename: Erkka
authors.initials: E
authors.lastname: Syvälahti
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
mesh_terms: D000662:Amphetamines / Q000378:metabolism; D000818:Animals; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D015290:Second Messenger Systems; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000662:Amphetamines; D015283:Citalopram; D004873:Ergolines; D005473:Fluoxetine; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C031649:mesulergine