Journal
JOURNAL OF PSYCHOPHARMACOLOGY
Volume 16, Issue 4, Pages 297-304Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/026988110201600403
Keywords
antidepressants; desipramine; fluoxetine; microdialysis; paroxetine; venlafaxine
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The present study employed in-vivo microdialysis techniques in the freely moving rat to systematically compare the neurochemical effects of various antidepressant agents on extracellular concentrations of norepinephrine (NE) and serotonin (5-HT) in the frontal cortex. We found that acute administration of the tricyclic antidepressant, desipramine (3-30 mg/kg, S.C.) and the dual serotonin/norepinephrine reuptake inhibitor, venlafaxine (3-120 mg/kg, s.c.), produced dose-dependent and robust increases in cortical NE concentrations (498% and 403%, respectively). Conversely, acute injection of the selective serotonin reuptake inhibitors, fluoxetine (30 mg/kg, s.c.) and paroxetine (1-10 mg/kg, s.c.), did not alter forebrain NE concentrations. However, paroxetine did produce a significant increase in cortical NE concentrations (164%) when administered at 30 mg/kg. These changes in NE were not paralleled by 5-HT, which showed no increase following administration of desipramine, venlafaxine, paroxetine or fluoxetine. Combination treatment with the 5-HT1A receptor antagonist, WAY-100635 (0.3 mg/kg, S.C.), significantly enhanced extracellular 5-HT concentrations following venlafaxine (10 and 30 mg/kg), fluoxetine (30 mg/kg) and paroxetine (3-30 mg/kg). Alternatively, WAY-100635 produced no augmentation of the antidepressant-induced changes in extracellular NE. Collectively, these studies show that paroxetine, at low to intermediate doses, and fluoxetine are selective for 5-HT versus NE systems, whereas venlafaxine produces similar effects on both 5-HT and NE levels at the effective doses tested.
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