English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/34678
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine

AuthorsMarek, Gerard J.; Martín-Ruiz, Raúl; Abo, Allyson; Artigas, Francesc
KeywordsM100907
5-HT2A receptors
Fluoxetine
DRL 72-s
Antidepressant
SSRIs
Issue DateDec-2005
PublisherNature Publishing Group
CitationNeuropsychopharmacology 30 (12) : 2205-2215 (2005)
AbstractThe addition of low doses of atypical antipsychotic drugs, which saturate 5-HT2A receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT2A receptor antagonist (M100907; formerly MDL 100,907) and low doses of a SSRI using a behavioral screen in rodents (the differential-reinforcement-of low rate 72-s schedule of reinforcement; DRL 72-s) which previously has been shown to be sensitive both to 5-HT2 antagonists and SSRIs. M100907 has a 100-fold or greater selectivity at 5-HT2A receptors vs other 5-HT receptor subtypes, and would not be expected to appreciably occupy non-5-HT2A receptors at doses below 100 g/kg. M100907 increased the reinforcement rate, decreased the response rate, and shifted the inter-response time distributions to the right in a pattern characteristic of antidepressant drugs. In addition, a positive synergistic interaction occurred when testing low doses of the 5-HT2A receptor antagonist (6.25–12.5 g/kg) with clinically relevant doses of the SSRI fluoxetine (2.5–5 mg/kg), which both exerted minimal antidepressant-like effects by themselves. In vivo microdialysis study revealed that a low dose of M100907 (12.5 g/kg) did not elevate extracellular 5-HT levels in the prefrontal cortex over those observed with fluoxetine alone (5 mg/kg). These results will be discussed in the context that the combined blockade of 5-HT2A receptors and serotonin transporters (SERT) may result in greater efficacy in treating neuropsychiatric syndromes than blocking either site alone.
Publisher version (URL)http://dx.doi.org/10.1038/sj.npp.1300762
URIhttp://hdl.handle.net/10261/34678
DOI10.1038/sj.npp.1300762
ISSN0893-133X
E-ISSN1740-634X
Appears in Collections:(IIBB) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.