Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/34793
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Monoamine oxidase inhibitors increase preferentially extracellular 5-hydroxytryptamine in the midbrain raphe nuclei. A brain microdialysis study in the awake rat

AuthorsCelada, Pau CSIC ORCID; Artigas, Francesc CSIC ORCID
KeywordsSerotonin release
Raphe nuclei
Monoamine oxidase inhibitors
Intracerebral microdialysis
Antidepressants
Issue DateJun-1993
PublisherSpringer
CitationNaunyn Schmiedeberg's Archives of Pharmacology 347 (6) : 583-590 (1993)
AbstractWe have examined the local and systemic effects of clorgyline, tranylcypromine and deprenyl on extracellular serotonin (5-HT) and 5-hydroxyindoleacetic acid in the raphe nuclei and in frontal cortex of awake, freely-moving rats using microdialysis. When administered through the dialysis probe, monoamine oxidase (monoamine: oxygen oxidoreductase (deaminating), E.C. 1.4.3.4., MAO) inhibitors increased 5-HT output in a dose-dependent manner in both brain areas. The effects were more pronounced in the raphe nuclei for the three MAO inhibitors at all doses assayed. When the monoamine oxidase inhibitors were given i.p., dialysate 5-HT increased dramatically, after tranylcypromine (15 mg/kg), in raphe nuclei and frontal cortex (area under the curve (AUC) to 4 h post-treatment: 63-fold and 11-fold, respectively) whereas the effects of clorgyline (10 mg/kg) were much less pronounced (+ 47% increase in the AUC for raphe nuclei, P < 0.09;="" +="" 18%="" increase="" in="" the="" auc="" for="" frontal="" cortex,="" n.s.).="" deprenyl="" (2.5="" mg/kg,="" i.p.)="" induced="" a="" moderate="" (+="" 22%)="" increase="" of="" dialysate="" 5-ht="" from="" the="" raphe="" nuclei="" but="" did="" not="" cause="" a="" change="" in="" dialysate="" 5-ht="" from="" the="" frontal="" cortex="" (+="" 4%).="" however,="" clorgyline,="" or="" deprenyl,="" dramatically="" increased="" dialysate="" 5-ht="" in="" animals="" which="" had="" been="" pre-treated="" with="" the="" above="" dose="" of="" deprenyl,="" or="" clorgyline,="" respectively,="" showing="" that="" the="" blockade="" of="" both="" forms="" of="" mao="" results="" in="" much="" larger="" increases="" of="" extracellular="" 5-ht="" than="" does="" the="" blockade="" of="" either="" form=""> These results indicate that: (a) deamination by MAO participates actively in the control of the extracellular concentration of 5-HT in those areas of the brain that are rich in serotoninergic nerve terminals as well as in cell bodies, (b) in vivo, brain 5-HT is deaminated preferentially by MAO-A but its full inhibition does not result in an increased release of 5-HT, in spite of a large accumulation of 5-HT in the brain tissue, (c) MAO-B deaminates 5-HT when the A-form is inhibited (in this situation, MAO-B participates actively in the control of a releasable pool of 5-HT), (d) the raphe nuclei appears to be a preferential site of action of MAO inhibitors, administered either locally or systemically. These results may help to understand the model of action of MAO inhibitors as antidepressant drugs.
DescriptionThe final publication is available at www.springerlink.com
Publisher version (URL)http://dx.doi.org/10.1007/BF00166940
URIhttp://hdl.handle.net/10261/34793
DOI10.1007/BF00166940
ISSN0028-1298
E-ISSN1432-1912
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

SCOPUSTM   
Citations

91
checked on May 12, 2022

WEB OF SCIENCETM
Citations

85
checked on May 13, 2022

Page view(s)

323
checked on May 17, 2022

Download(s)

117
checked on May 17, 2022

Google ScholarTM

Check

Altmetric

Dimensions


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