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Title

Effect of fluoxetine on extracellular 5-hydroxytryptamine in the rat brain. Role of 5-HT autoreceptors

AuthorsHervás, Ildefonso; Artigas, Francesc CSIC ORCID
Keywords5-HT receptors
Antidepressant
Dorsal raphe nucleus
Median raphe nucleus
Microdialysis
5-HT (5-hydroxytryptamine, serotonin) uptake
Issue Date25-Sep-1998
PublisherElsevier
CitationEuropean Journal of Pharmacology 358 (1) : 9-18 (1998)
AbstractUsing microdialysis, we examined the effects of the antidepressant drug fluoxetine on 5-hydroxytryptamine (5-HT) output in rat brain. Fluoxetine (1, 3 and 10 mg/kg i.p.) dose dependently increased 5-HT output in the dorsal and median raphe nuclei and four forebrain areas. Maximal elevations were noted in the raphe nuclei. At 1 and 3 mg/kg, fluoxetine elicited minor or no increases of 5-HT output in the forebrain. When citalopram was present in the perfusion fluid, fluoxetine (10 mg/kg) reduced 5-HT output, an effect reversed by the administration of the selective 5-HT1A receptor antagonist ¿N-[2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl]-N-(2-pyridyl) cyclohexane carboxamide.3HCl¿ (WAY 100635). This reduction was more marked in the frontal cortex than in the dorsal hippocampus. Consistent with this, WAY 100635 potentiated the effect of 3 and 10 mg/kg fluoxetine more in the frontal cortex than in the dorsal hippocampus. The administration of a combination of WAY 100635 (0.3 mg/kg s.c.) and the 5-HT1B/1D receptor antagonist ¿N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl),[1,1-biphenyl]-4-carboxiamide¿ (GR 127935; 5 mg/kg s.c.) potentiated the effect of 3 mg/kg fluoxetine to an extent similar to that of WAY 100635 alone in both areas. These results suggest that somatodendritic 5-HT1A receptors offset the effect of fluoxetine in the frontal cortex but not (or to a lesser extent) in the dorsal hippocampus. GR 127935 may have a partial antagonistic action at terminal 5-HT autoreceptors in vivo.
Publisher version (URL)http://dx.doi.org/10.1016/S0014-2999(98)00579-2
URIhttp://hdl.handle.net/10261/34753
DOI10.1016/S0014-2999(98)00579-2
ISSN0014-2999
E-ISSN1879-0712
Appears in Collections:(IIBB) Artículos




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