Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration.
An increase in central postsynaptic 5-hydroxytryptamine (5-HT) function activates expression of activity-related cytoskeletal protein (Arc). Here, Arc expression was used to test whether, in rats, co-administration of a 5-HT re-uptake inhibitor (paroxetine) and a 5-HT1A receptor antagonist (WAY 1006...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797057017269977088 |
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| author | Castro, E Tordera, R Hughes, Z Pei, Q Sharp, T |
| author_facet | Castro, E Tordera, R Hughes, Z Pei, Q Sharp, T |
| author_sort | Castro, E |
| collection | OXFORD |
| description | An increase in central postsynaptic 5-hydroxytryptamine (5-HT) function activates expression of activity-related cytoskeletal protein (Arc). Here, Arc expression was used to test whether, in rats, co-administration of a 5-HT re-uptake inhibitor (paroxetine) and a 5-HT1A receptor antagonist (WAY 100635) increases postsynaptic 5-HT function. After pre-treatment with WAY 100635 (0.3 mg/kg s.c.), paroxetine (5 mg/kg s.c.) caused a threefold increase in 5-HT in prefrontal cortex microdialysates. In situ hybridization studies found that neither paroxetine (5 mg/kg s.c.) nor WAY 1000635 (0.3 mg/kg s.c.) altered Arc mRNA abundance in any region examined. In contrast, paroxetine (5 mg/kg s.c.) increased Arc mRNA after pre-treatment with WAY 100635 (0.3 mg/kg s.c.). This increase was apparent in cortical regions (frontal, parietal and cingulate) and caudate nucleus but was absent in hippocampus (CA1). Increases in Arc mRNA were accompanied by an increase in c-fos mRNA. The increase in Arc expression induced by paroxetine/WAY 100635 was abolished by the 5-HT synthesis inhibitor, p-chlorophenylalanine (300 mg/kg i.p., daily for two days). In conclusion, paroxetine and WAY 100635 injected in combination (but not alone) caused a region-specific, 5-HT-mediated increase in Arc expression. These data provide molecular evidence that co-administration of a 5-HT re-uptake inhibitor and 5-HT1A receptor antagonist increases 5-HT function at the postsynaptic level. |
| first_indexed | 2024-03-06T19:30:30Z |
| format | Journal article |
| id | oxford-uuid:1d49a149-88aa-4a20-b016-34b985be0173 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:30:30Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:1d49a149-88aa-4a20-b016-34b985be01732022-03-26T11:10:02ZUse of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d49a149-88aa-4a20-b016-34b985be0173EnglishSymplectic Elements at Oxford2003Castro, ETordera, RHughes, ZPei, QSharp, TAn increase in central postsynaptic 5-hydroxytryptamine (5-HT) function activates expression of activity-related cytoskeletal protein (Arc). Here, Arc expression was used to test whether, in rats, co-administration of a 5-HT re-uptake inhibitor (paroxetine) and a 5-HT1A receptor antagonist (WAY 100635) increases postsynaptic 5-HT function. After pre-treatment with WAY 100635 (0.3 mg/kg s.c.), paroxetine (5 mg/kg s.c.) caused a threefold increase in 5-HT in prefrontal cortex microdialysates. In situ hybridization studies found that neither paroxetine (5 mg/kg s.c.) nor WAY 1000635 (0.3 mg/kg s.c.) altered Arc mRNA abundance in any region examined. In contrast, paroxetine (5 mg/kg s.c.) increased Arc mRNA after pre-treatment with WAY 100635 (0.3 mg/kg s.c.). This increase was apparent in cortical regions (frontal, parietal and cingulate) and caudate nucleus but was absent in hippocampus (CA1). Increases in Arc mRNA were accompanied by an increase in c-fos mRNA. The increase in Arc expression induced by paroxetine/WAY 100635 was abolished by the 5-HT synthesis inhibitor, p-chlorophenylalanine (300 mg/kg i.p., daily for two days). In conclusion, paroxetine and WAY 100635 injected in combination (but not alone) caused a region-specific, 5-HT-mediated increase in Arc expression. These data provide molecular evidence that co-administration of a 5-HT re-uptake inhibitor and 5-HT1A receptor antagonist increases 5-HT function at the postsynaptic level. |
| spellingShingle | Castro, E Tordera, R Hughes, Z Pei, Q Sharp, T Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title | Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title_full | Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title_fullStr | Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title_full_unstemmed | Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title_short | Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration. |
| title_sort | use of arc expression as a molecular marker of increased postsynaptic 5 ht function after ssri 5 ht1a receptor antagonist co administration |
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