کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9416000 1614328 2005 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of continuous administration of paroxetine on ligand binding site and expression of serotonin transporter protein in mouse brain
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Effects of continuous administration of paroxetine on ligand binding site and expression of serotonin transporter protein in mouse brain
چکیده انگلیسی
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 μmol/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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1053, Issues 1–2, 16 August 2005, Pages 154-161
نویسندگان
, , , , , , ,