Linked Life Data

16051196

Source:http://linkedlifedata.com/resource/pubmed/id/16051196

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2005-8-12
pubmed:abstractText
Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, are utilized in the treatment of depression and anxiety disorders. Although SSRIs potently interfere with the activity of brain serotonin transporter (SERT) after acute treatment, clinical improvement of psychiatric diseases is observed only after the repeated administration for several weeks (2-6 weeks). The present study was undertaken to investigate the effects of continuous administration of paroxetine on specific [3H]paroxetine binding sites and expression of SERT protein in mouse brain. Mice continuously and subcutaneously received paroxetine at doses of 2.67 or 13.3 mumol/kg/day for 21 days by using osmotic minipumps, and the steady-state plasma drug levels were within the range of reported concentrations in the clinical therapy. Continuous administration of paroxetine at theses doses produced significant (25-46%) reduction of [3H]paroxetine binding in each brain region (cerebral cortex, striatum, hippocampus, thalamus, midbrain) of mice. In Western blot analysis, expression levels of SERT protein in the thalamus and midbrain of mice were significantly (51% and 61%, respectively) decreased on day 21 after the implantation of minipumps at the higher dose. In conclusion, this study has firstly shown that continuous administration of paroxetine induces significant reduction of not only ligand binding sites of SERT but the protein expression level in mouse brain. Such down-regulation of SERT may partly underlie the therapeutic effect of long-term treatment with SSRIs in human.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
1053
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
154-61
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16051196-Analysis of Variance, pubmed-meshheading:16051196-Animals, pubmed-meshheading:16051196-Binding Sites, pubmed-meshheading:16051196-Blotting, Western, pubmed-meshheading:16051196-Brain, pubmed-meshheading:16051196-Brain Chemistry, pubmed-meshheading:16051196-Cell Line, pubmed-meshheading:16051196-Chromatography, High Pressure Liquid, pubmed-meshheading:16051196-Dose-Response Relationship, Drug, pubmed-meshheading:16051196-Drug Administration Schedule, pubmed-meshheading:16051196-Gene Expression Regulation, pubmed-meshheading:16051196-Humans, pubmed-meshheading:16051196-Ligands, pubmed-meshheading:16051196-Male, pubmed-meshheading:16051196-Membrane Glycoproteins, pubmed-meshheading:16051196-Membrane Transport Proteins, pubmed-meshheading:16051196-Mice, pubmed-meshheading:16051196-Mice, Inbred ICR, pubmed-meshheading:16051196-Nerve Tissue Proteins, pubmed-meshheading:16051196-Paroxetine, pubmed-meshheading:16051196-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:16051196-Serotonin Uptake Inhibitors, pubmed-meshheading:16051196-Time Factors, pubmed-meshheading:16051196-Tritium
pubmed:year
2005
pubmed:articleTitle
Effects of continuous administration of paroxetine on ligand binding site and expression of serotonin transporter protein in mouse brain.
pubmed:affiliation
Department of Biopharmaceutical Sciences and Center of Excellence (COE) Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
pubmed:publicationType
Journal Article, Comparative Study