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In vivo potentiation of reboxetine and citalopram effect on extracellular noradrenaline in rat brain by α2-adrenoceptor antagonism.
Ortega, Jorge E; Fernández-Pastor, Begoña; Callado, Luis F; Meana, J Javier.
Afiliación
  • Ortega JE; Department of Pharmacology, University of the Basque Country (UPV/EHU), Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, 48940 Leioa, Bizkaia, Spain. jorge.ortega@ehu.es
Eur Neuropsychopharmacol ; 20(11): 813-22, 2010 Nov.
Article en En | MEDLINE | ID: mdl-20813509
The therapeutic activity of noradrenaline reuptake inhibitors (NaRIs) and serotonin reuptake inhibitors (SSRIs) as antidepressant is based on their ability to increase monoamine concentrations in the synaptic cleft. α(2)-Adrenoceptors inhibit noradrenaline (NA) release, which modulates antidepressant neurochemical activity. The present study assesses the influence of the addition of the selective α(2)-adrenoceptor antagonist RS79948 to the NaRI reboxetine and the SSRI citalopram on brain extracellular NA. Dual-probe microdialysis technique in the locus coeruleus (LC) and prefrontal cortex (PFC) was performed in freely moving rats. Acute reboxetine (3 and 5 mg/kg i.p.) promoted a dose-dependent increase of NA in LC (164 ± 15%; 243 ± 24%) and PFC (140 ± 7%; 181 ± 30%). Acute citalopram (5 mg/kg i.p.) did not change NA in LC or PFC, but at 10 mg/kg i.p. increased NA in LC (144 ± 14%) and decreased it in PFC (-42 ± 7%). An inactive dose of RS79948 (0.1mg/kg i.p.) in rats pretreated with reboxetine (3 mg/kg i.p.) or citalopram (5mg/kg i.p.) induced a significant enhancement of NA in LC (reboxetine: 462 ± 137%; citalopram: 142 ± 11%) and PFC (reboxetine: 281 ± 56%; citalopram: 130 ± 16%). The results indicate that co-administration of selective α(2)-adrenoceptor antagonist drugs might improve the effects of NaRI or SSRI antidepressants by enhancing extracellular NA concentrations in the brain.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Citalopram / Norepinefrina / Morfolinas / Espacio Extracelular / Antagonistas de Receptores Adrenérgicos alfa 2 Límite: Animals Idioma: En Revista: Eur Neuropsychopharmacol Asunto de la revista: PSICOFARMACOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: España Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Citalopram / Norepinefrina / Morfolinas / Espacio Extracelular / Antagonistas de Receptores Adrenérgicos alfa 2 Límite: Animals Idioma: En Revista: Eur Neuropsychopharmacol Asunto de la revista: PSICOFARMACOLOGIA Año: 2010 Tipo del documento: Article País de afiliación: España Pais de publicación: Países Bajos