Abstract
Reboxetine is a selective noradrenergic reuptake inhibitor that displays an antidepressant profile in both animal tests and in clinical trials. The present study examined the ability of reboxetine to alter stress-induced increases in norepinephrine, serotonin and dopamine efflux in the frontal cortex in awake behaving rats. Acute systemic administration of reboxetine (0.3–20.0 mg/kg) dose-dependently increased extracellular norepinephrine in the frontal cortex while having no effect on extracellular serotonin. At 20 mg/kg, reboxetine also increased extracellular dopamine. Application of a 20-min tailpinch stress increased extracellular norepinephrine. This effect was greatly potentiated in rats pretreated with reboxetine. Tailpinch did not elicit increases in dopamine in saline treated animals but this stimulus increased dopamine levels following reboxetine pretreatment. Furthermore, chronic administration of reboxetine for 14 days resulted in elevated basal concentrations of extracellular norepinephrine and dopamine and a greater net increase of extracellular norepinephrine and dopamine, but not serotonin, in response to tailpinch compared with vehicle control animals. Taken together, these data support the view that the noradrenergic and dopaminergic systems are modified by reboxetine treatment and may be important factors in the mechanism of action of antidepressant compounds.
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Acknowledgements
This work was supported by USPHS Grant MH61418 (MEP) and a research grant from Pharmacia & Upjohn, Kalamazoo, MI (MEP). The authors thank Dr. John Cryan for helpful discussions and Kevin Brown for technical assistance. We gratefully acknowledge the assistance of Jennifer Jannace of Triangle Laboratories for analysis of plasma reboxetine levels.
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Page, M., Lucki, I. Effects of Acute and Chronic Reboxetine Treatment on Stress-induced Monoamine Efflux in the Rat Frontal Cortex. Neuropsychopharmacol 27, 237–247 (2002). https://doi.org/10.1016/S0893-133X(02)00301-9
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DOI: https://doi.org/10.1016/S0893-133X(02)00301-9
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