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dc.contributor.authorMarek, Gerard J.-
dc.contributor.authorMartín-Ruiz, Raúl-
dc.contributor.authorAbo, Allyson-
dc.contributor.authorArtigas, Francesc-
dc.date.accessioned2011-04-15T07:17:18Z-
dc.date.available2011-04-15T07:17:18Z-
dc.date.issued2005-12-
dc.identifier.citationNeuropsychopharmacology 30 (12) : 2205-2215 (2005)es_ES
dc.identifier.issn0893-133X-
dc.identifier.urihttp://hdl.handle.net/10261/34678-
dc.description.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.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsclosedAccesses_ES
dc.subjectM100907es_ES
dc.subject5-HT2A receptorses_ES
dc.subjectFluoxetinees_ES
dc.subjectDRL 72-ses_ES
dc.subjectAntidepressantes_ES
dc.subjectSSRIses_ES
dc.titleThe selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetinees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1038/sj.npp.1300762-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1038/sj.npp.1300762es_ES
dc.identifier.e-issn1740-634X-
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