Effects of acute and chronic reboxetine treatment on stress-induced monoamine efflux in the rat frontal cortex.
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.
Page
Michelle E
ME
Department of Psychiatry, University of Pennsylvania, 538 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA. page@drexel.edu
Lucki
Irwin
I
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D009025:Morpholines; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; D000077593:Reboxetine; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine