Research article summary (published 29 Nov 2002):

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

Full 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.

Author information

Author/s: Beyer, Chad E (CE); Boikess, Steve (S); Luo, Bin (B); Dawson, Lee A (LA);

Affiliation: Neuroscience Discovery Research, Wyeth Research, Princeton, New Jersey 08543-8000, USA. beyerc1(-atsign-)wyeth.com

Journal and publication information

Publication Type: Comparative Study; Journal Article

Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol), published in United States. (Language: eng)

Reference: 2002-Dec; vol 16 (issue 4) : pp 297-304

Dates: Created 2002/12/30; Completed 2003/05/19; Revised 2006/11/15;

PMID: 12503828, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antidepressive Agents - pharmacology Antidepressive Agents, Tricyclic - pharmacology Cyclohexanols - pharmacology Desipramine - pharmacology Dose-Response Relationship, Drug Drug Interactions Extracellular Space - drug effects; metabolism Fluoxetine - pharmacology Male Microdialysis Norepinephrine - metabolism

Norepinephrine - metabolism Paroxetine - pharmacology Piperazines - pharmacology Prefrontal Cortex - drug effects; metabolism Pyridines - pharmacology Rats Rats, Sprague-Dawley Receptors, Serotonin - drug effects Receptors, Serotonin, 5-HT1 Serotonin - metabolism Serotonin Antagonists - pharmacology Serotonin Uptake Inhibitors - pharmacology

Associated Chemicals: Antidepressive Agents (0) ; Antidepressive Agents, Tricyclic (0) ; Cyclohexanols (0) ; Piperazines (0) ; Pyridines (0) ; Receptors, Serotonin (0) ; Receptors, Serotonin, 5-HT1 (0) ; Serotonin Antagonists (0) ; Serotonin Uptake Inhibitors (0) ; WAY 100635 (146714-97-8) ; Desipramine (50-47-5) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Fluoxetine (54910-89-3) ; Paroxetine (61869-08-7) ; venlafaxine (93413-69-5)

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