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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1997-3-19
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pubmed:abstractText |
The serotonin (5-HT)-increasing action of 5-HT uptake or monoamine oxidase inhibitors is limited by a negative feedback at somatodendritic level. The excess 5-HT produced by these antidepressant drugs in the interstitial space of the midbrain raphe activates somatodendritic 5-HT1A autoreceptors, thereby attenuating terminal 5-HT release. This effect is maximal in forebrain areas innervated by the dorsal raphe nucleus and can be prevented by the administration of non-selective [(-)pindolol, (-)tertatolol] and selective (WAY-100635) 5-HT1A antagonists. In keeping with these observations, the combined administration of selective serotonin reuptake inhibitors (SSRIs) and 5-HT1A antagonists increase the cortical and striatal extracellular 5-HT concentration more than the former alone. Also, concurrent inhibition of the 5-HT and noradrenaline transporters with 20 mg/kg imipramine increases cortical extracellular 5-HT concentration more than SSRI doses which maximally block the 5-HT transporter. Moreover, the effects of fluoxetine on frontal cortex 5-HT are potentiated by a dose of desipramine that does not modify extracellular 5-HT by itself. Given the relevance of increased serotonergic transmission in the treatment of depression, these experimental data indicate that dual-action antidepressant treatments may be more effective than those which selectively inhibit the 5-HT transporter.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0268-1315
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
11 Suppl 4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8923121-Animals,
pubmed-meshheading:8923121-Brain,
pubmed-meshheading:8923121-Depressive Disorder,
pubmed-meshheading:8923121-Humans,
pubmed-meshheading:8923121-Microdialysis,
pubmed-meshheading:8923121-Receptors, Serotonin,
pubmed-meshheading:8923121-Serotonin,
pubmed-meshheading:8923121-Serotonin Antagonists,
pubmed-meshheading:8923121-Serotonin Uptake Inhibitors
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pubmed:year |
1996
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pubmed:articleTitle |
Two actions are better than one: avoiding self-inhibition of serotonergic neurones enhances the effects of serotonin uptake inhibitors.
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pubmed:affiliation |
Department of Neurochemistry, Instituto de Investigaciones Biomédicas de Barcelona, CSIC.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Review,
Research Support, Non-U.S. Gov't
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