Comparison of the effects of antidepressants on norepinephrine and serotonin concentrations in the rat frontal cortex: an in-vivo microdialysis study

• Published in: Journal of psychopharmacology (Oxford) Vol. 16; no. 4; p. 297
• Main Authors: Beyer, Chad E, Boikess, Steve, Luo, Bin, Dawson, Lee A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2002
• Subjects: Animals; Antidepressive Agents - pharmacology; Antidepressive Agents, Tricyclic - pharmacology; Cyclohexanols - pharmacology; Desipramine - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Extracellular Space - drug effects; Extracellular Space - metabolism; Fluoxetine - pharmacology; Male; Microdialysis; Norepinephrine - metabolism; Paroxetine - pharmacology; Piperazines - pharmacology; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - drug effects; Receptors, Serotonin, 5-HT1; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Venlafaxine Hydrochloride
• ISSN: 0269-8811
• DOI: 10.1177/026988110201600403

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 (3-30 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.