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http://purl.uniprot.org/citations/12172696http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12172696http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Serotonin (5-HT) autoreceptors regulate extracellular 5-HT levels and have been suggested to limit the effects of acute treatment with selective serotonin reuptake inhibitors (SSRIs).

Objectives

The role of terminal 5-HT(1B) autoreceptors was assessed by comparing the effects of a SSRI on extracellular 5-HT in wild-type and 5-HT(1B) receptor knockout (KO) mice and by using a 5-HT(1B) receptor antagonist. Since systemic SSRI administration also activates somatodendritic 5-HT(1A) autoreceptors, a SSRI was administered locally to study the role of terminal 5-HT(1B) autoreceptors.

Methods

In vivo microdialysis in wild-type and 5-HT(1B) receptor KO mice was used to study the effects of the 5-HT(1B) receptor agonist CP93129 (1 micro M), the SSRI fluvoxamine (0.3 micro M and 1.0 micro M) and the 5-HT(1B) receptor antagonist NAS-181 (1 micro M) on extracellular 5-HT in the medial prefrontal cortex.

Results

The 5-HT increase induced by local SSRI administration was augmented in 5-HT(1B) KO mice relative to wild-type mice and was augmented by simultaneous administration of a 5-HT(1B) receptor antagonist in the latter genotype. Basal 5-HT levels did not differ between the two genotypes. Activation of 5-HT(1B) receptors by CP93129 decreased extracellular 5-HT, whereas 5-HT levels in wild-type mice were not affected by the 5-HT(1B) receptor antagonist NAS-181. In 5-HT(1B) KO mice, NAS-181 did not affect extracellular 5-HT and did not further increase the effect of fluvoxamine, showing that NAS-181 is a selective 5-HT(1B) receptor antagonist. The greater increase in 5-HT levels following combined administration of a SSRI with NAS-181 in wild-type mice, relative to 5-HT(1B) KO mice, suggests possible adaptive changes in the KO mice.

Conclusions

The present study shows that terminal 5-HT(1B) autoreceptors play a significant role in the regulation of 5-HT release in the prefrontal cortex."xsd:string
http://purl.uniprot.org/citations/12172696http://purl.org/dc/terms/identifier"doi:10.1007/s00213-002-1117-z"xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/author"Olivier B."xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/author"Westenberg H.G."xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/author"de Groote L."xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/date"2002"xsd:gYear
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/name"Psychopharmacology (Berl)"xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/pages"419-424"xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/title"Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice."xsd:string
http://purl.uniprot.org/citations/12172696http://purl.uniprot.org/core/volume"162"xsd:string
http://purl.uniprot.org/citations/12172696http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12172696
http://purl.uniprot.org/citations/12172696http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12172696
http://purl.uniprot.org/uniprot/#_P28334-mappedCitation-12172696http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12172696
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http://purl.uniprot.org/uniprot/P28334http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/12172696
http://purl.uniprot.org/uniprot/Q0VES5http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/12172696