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Comparison of the effects of antidepressants on norepinephrine and serotonin concentrations in the rat frontal cortex: an in-vivo microdialysis study.
- Source :
-
Journal of psychopharmacology (Oxford, England) [J Psychopharmacol] 2002 Dec; Vol. 16 (4), pp. 297-304. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Animals
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
Paroxetine pharmacology
Piperazines pharmacology
Prefrontal Cortex drug effects
Pyridines pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Serotonin drug effects
Receptors, Serotonin, 5-HT1
Serotonin Antagonists pharmacology
Selective Serotonin Reuptake Inhibitors pharmacology
Venlafaxine Hydrochloride
Antidepressive Agents pharmacology
Norepinephrine metabolism
Prefrontal Cortex metabolism
Serotonin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0269-8811
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of psychopharmacology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 12503828
- Full Text :
- https://doi.org/10.1177/026988110201600403