In vivo potentiation of reboxetine and citalopram effect on extracellular noradrenaline in rat brain by a sub(2)-adrenoceptor antagonism

• Published in: European neuropsychopharmacology Vol. 20; no. 11; pp. 813 - 822
• Main Authors: Ortega, Jorge E, Fernandez-Pastor, Begona, Callado, Luis F, Meana, JJavier
• Format: Journal Article
• Language: English
• Published: 01.11.2010
• Subjects: Antagonism
• ISSN: 0924-977X
• DOI: 10.1016/j.euroneuro.2010.07.008

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. a sub(2)-Adrenoceptors inhibit noradrenaline (NA) release, which modulates antidepressant neurochemical activity. The present study assesses the influence of the addition of the selective a sub(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 (0.1 mg/kg i.p.) in rats pretreated with reboxetine (3 mg/kg i.p.) or citalopram (5 mg/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 a sub(2)-adrenoceptor antagonist drugs might improve the effects of NaRI or SSRI antidepressants by enhancing extracellular NA concentrations in the brain.