Cited by 156Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionNeuroscience and Neuropharmacology Research

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Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats

Li, Simon Xi-Ming, Perry, Kenneth W, Wong, David T·2002·Neuropharmacology

DOI 10.1016/s0028-3908(01)00160-5

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Abstract

The finding that serotonin (5-HT) can modulate dopamine (DA) and norepinephrine (NE) release in the brain has led us to hypothesize that fluoxetine, a selective 5-HT reuptake inhibitor, may influence the ability of bupropion, a preferential DA and NE dual reuptake inhibitor, to modulate extracellular DA and NE concentrations in some brain areas. The present study was designed to evaluate this hypothesis by assessing the effects of fluoxetine on bupropion-induced changes in extracellular monoamine concentrations by means of in vivo microdialysis. Three mesocorticolimbic areas including hypothalamus (Ht), prefrontal cortex (Pfc) and nucleus accumbens (Acb) were selected based on their relevance to depression and antidepressant actions. In the Ht of untreated rats, bupropion dose-dependently (s.c.) increased extracellular DA and NE concentrations either in single injection study or in sequential injection study. Thus, 10 mg/kg of bupropion had no effect on the DA and NE concentrations, while 30 mg/kg of bupropion induced transient but significant increases (about 240% of the baselines), and 100 mg/kg of bupropion induced marked and persistent increases (over 600% of the baselines) in the DA and NE concentrations. In the rats pre-treated with fluoxetine (10 mg/kg, s.c., 90 min interval), the threshold dose of bupropion (10 mg/kg) significantly increased the DA and NE concentrations to more than 350% of the baselines, and 30 mg/kg of bupropion markedly increased the DA and NE concentrations to more than 570% of the baselines in the Ht. The fluoxetine pre-treatment also potentiated the DA increases induced by 10 mg/kg of bupropion in the Pfc (260% for bupropion alone vs 357% for the combination) and in the Acb (224% vs 645%). The bupropion-induced NE increases were potentiated by fluoxetine mainly in the Ht. Bupropion did not significantly affect the extracellular 5-HT concentrations in all the 3 brain areas tested. In summary, the present study demonstrated that bupropion can increase extracellular DA and NE concentrations in several mesocorticolimbic areas, which may have an impact on bupropion's antidepressant actions. Furthermore, fluoxetine can potentiate the bupropion-induced DA and NE increases, which may produce more effective and rapid antidepressant actions.

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Authors: Li, S. X.-M., Perry, K. W., & Wong, D. T.
Affiliations: Eli Lilly (United States) (US)
Corresponding author: Perry, Kenneth W
ORCID: Wong, David T
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2002-02
Volume: 42
Issue: 2
Pages: 181-190
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/s0028-3908(01)00160-5
OpenAlex: W1971669832
Cited by: 156
References: 60
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 14 · 2012: 11
FWCI: 3.95
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: fluoxetine, bupropion, extracellular dopamine, serotonin, mesocorticolimbic system, hypothalamus, prefrontal cortex, nucleus accumbens, monoamine release, antidepressant mechanism, selective serotonin reuptake inhibitors, depression, drug interactions, microdialysis, rats
MeSH terms: Animals, Cerebral Cortex, Chromatography, High Pressure Liquid, Dopamine, Extracellular Space, Fluoxetine, Hematocrit, Limbic System, Male, Norepinephrine, Bupropion, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Microdialysis, Dopamine Uptake Inhibitors, Rats

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Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats

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