Source:http://linkedlifedata.com/resource/pubmed/id/21277875
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2011-6-7
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| pubmed:abstractText |
The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism/antagonism of 5-HT receptors should be considered in the search of therapeutic targets for treating this serious disorder.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-Hydroxytryptophan,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RS 127445,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2B,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin 5-HT1 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin 5-HT2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin 5-HT2 Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1873-7064
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
61
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
495-502
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| pubmed:meshHeading |
pubmed-meshheading:21277875-5-Hydroxytryptophan,
pubmed-meshheading:21277875-Animals,
pubmed-meshheading:21277875-Behavior, Animal,
pubmed-meshheading:21277875-Depression,
pubmed-meshheading:21277875-Dose-Response Relationship, Drug,
pubmed-meshheading:21277875-Exploratory Behavior,
pubmed-meshheading:21277875-Male,
pubmed-meshheading:21277875-Mice,
pubmed-meshheading:21277875-Mice, 129 Strain,
pubmed-meshheading:21277875-Mice, Transgenic,
pubmed-meshheading:21277875-Motor Activity,
pubmed-meshheading:21277875-Pyrimidines,
pubmed-meshheading:21277875-Random Allocation,
pubmed-meshheading:21277875-Receptor, Serotonin, 5-HT1B,
pubmed-meshheading:21277875-Receptor, Serotonin, 5-HT2B,
pubmed-meshheading:21277875-Serotonin,
pubmed-meshheading:21277875-Serotonin 5-HT1 Receptor Agonists,
pubmed-meshheading:21277875-Serotonin 5-HT2 Receptor Agonists,
pubmed-meshheading:21277875-Serotonin 5-HT2 Receptor Antagonists,
pubmed-meshheading:21277875-Serotonin Receptor Agonists,
pubmed-meshheading:21277875-Serotonin Syndrome,
pubmed-meshheading:21277875-Serotonin Uptake Inhibitors
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| pubmed:year |
2011
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| pubmed:articleTitle |
Implication of 5-HT(2B) receptors in the serotonin syndrome.
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| pubmed:affiliation |
INSERM UMR-S 839, Université Pierre et Marie Curie, Institut du Fer à Moulin, 17 rue du Fer à Moulin, F75005 Paris, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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