Neuropsychopharmacology (New York, N.Y.), 2002-12, Vol.27 (6), p.949-959
2002
Details
- Autor(en) / Beteiligte
- Titel
- R-fluoxetine Increases Extracellular DA, NE, As Well As 5-HT in Rat Prefrontal Cortex and Hypothalamus: An in vivo Microdialysis and Receptor Binding Study
- Ist Teil von
- Neuropsychopharmacology (New York, N.Y.), 2002-12, Vol.27 (6), p.949-959
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 2002
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The selective serotonin reuptake inhibitor fluoxetine consists of equal amounts of R and S stereoisomers. In this study, we investigated the pharmacologic properties of the stereoisomers using transporter and receptor binding assays and in vivo microdialysis in freely moving rats. Binding to the transporter confirmed selectivity of R- and S-fluoxetine for the 5-HT transporter versus the dopamine (DA) and norepinephrine (NE) human transporters. Receptor binding studies demonstrated significant affinity of R-fluoxetine, but not S-fluoxetine, for human 5-HT2A and 5-HT2C receptor subtypes. Functional GTPγS binding studies indicated that R-fluoxetine is an antagonist at 5-HT2A and 5-HT2C receptors. In microdialysis studies, acute R- and S-fluoxetine increased extracellular levels of 5-HT, DA, and NE in prefrontal cortex (PFC), but R-fluoxetine caused significantly greater increases of catecholamines. R-fluoxetine increased extracellular levels of 5-HT and NE in PFC, nucleus accumbens, and hypothalamus, whereas it increased dopamine in PFC and hypothalamus, but not in DA-rich nucleus accumbens and striatum, thus indicating a regionally selective effect. The unexpected increases of extracellular catecholamines by a selective 5-HT uptake inhibitor like R-fluoxetine may be due to its antagonism of 5-HT2C receptors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0893-133XeISSN: 1740-634XDOI: 10.1016/S0893-133X(02)00377-9Titel-ID: cdi_proquest_miscellaneous_877591945
- Format
- –
- Schlagworte
- Animals, Antidepressant, Antidepressants, Biological and medical sciences, Catecholamines, Dogs, Dopamine, Dopamine - biosynthesis, Dose-Response Relationship, Drug, Electroconvulsive therapy, Extracellular Space - drug effects, Extracellular Space - metabolism, Fluoxetine - pharmacology, Humans, Hypothalamus, Hypothalamus - drug effects, Hypothalamus - metabolism, Laboratories, Male, Medical sciences, Mental depression, Microdialysis, Microdialysis - methods, Neuropharmacology, Neurosciences, Norepinephrine, Norepinephrine - biosynthesis, Pharmacology. Drug treatments, Prefrontal Cortex - drug effects, Prefrontal Cortex - metabolism, Protein Binding - drug effects, Protein Binding - physiology, Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease), Psychology. Psychoanalysis. Psychiatry, Psychopharmacology, R-Fluoxetine, Rats, Rats, Sprague-Dawley, Receptors, Serotonin - metabolism, Serotonin, Serotonin - biosynthesis, Stereoisomerism